この作品は、国立アレルギー·感染症研究所によってサポートされていましたCAGにP01 A1078894を付与します

<ol>
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G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathogen-mediated+inflammatory+atherosclerosis+is+mediated+in+part+via+Toll-like+receptor+2-induced+inflammatory+responses.">Pathogen-mediated inflammatory atherosclerosis is mediated in part via Toll-like receptor 2-induced inflammatory responses.</a> Journal of Innate Immunity. 2 (4), 334-343 (2010).</li><li>Hayashi, C., Papadopoulos, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Protective+role+for+TLR4+signaling+in+atherosclerosis+progression+as+revealed+by+infection+with+a+common+oral+pathogen.">Protective role for TLR4 signaling in atherosclerosis progression as revealed by infection with a common oral pathogen.</a> Journal of Immunology (Baltimore, Md.: 1950). 189 (7), 3681-3688 (2012).</li><li>Papadopoulos, G., Weinberg, E. O., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Macrophage-Specific+TLR2+Signaling+Mediates+Pathogen-Induced+TNF-Dependent+Inflammatory+Oral+Bone+Loss.">Macrophage-Specific TLR2 Signaling Mediates Pathogen-Induced TNF-Dependent Inflammatory Oral Bone Loss.</a> The Journal of Immunology. , (2012).</li><li>Gibson, F. C., Hong , C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Innate+immune+recognition+of+invasive+bacteria+accelerates+atherosclerosis+in+apolipoprotein+E-deficient+mice.">Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice.</a> Circulation. 109 (22), 2801-2806 (2004).</li><li>Miyamoto, T., Yumoto, H., Takahashi, Y., Davey, M., Gibson, F. C., Genco, C. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathogen-accelerated+atherosclerosis+occurs+early+after+exposure+and+can+be+prevented+via+immunization.">Pathogen-accelerated atherosclerosis occurs early after exposure and can be prevented via immunization.</a> Infection and Immunity. 74 (2), 1376-1380 (2006).</li><li>Baker, P. J., Dixon, M., Roopenian, D. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetic+control+of+susceptibility+to+Porphyromonas+gingivalis-induced+alveolar+bone+loss+in+mice.">Genetic control of susceptibility to Porphyromonas gingivalis-induced alveolar bone loss in mice.</a> Infection and Immunity. 68 (10), 5864-5868 (2000).</li><li>Baker, P. J., Dixon, M., Evans, R. T., Roopenian, D. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Heterogeneity+of+Porphyromonas+gingivalis+strains+in+the+induction+of+alveolar+bone+loss+in+mice.">Heterogeneity of Porphyromonas gingivalis strains in the induction of alveolar bone loss in mice.</a> Oral Microbiology and Immunology. 15 (1), 27-32 (2000).</li><li>Daugherty, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+models+of+atherosclerosis.">Mouse models of atherosclerosis.</a> The American Journal of the Medical Sciences. 323 (1), 3-10 (2002).</li><li>Weinreb, D. B., Aguinaldo, J. G. S., Feig, J. E., Fisher, E. A., Fayad, Z. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Non-invasive+MRI+of+mouse+models+of+atherosclerosis.">Non-invasive MRI of mouse models of atherosclerosis.</a> NMR in Biomedicine. 20 (3), 256-264 (2007).</li></ol>

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P.歯周経口感染モデルは、局所および全身の部位で病原体により誘導される慢性炎症の研究のための貴重なツールを提供します。このユニークなモデルは、慢性炎症や免疫病理に寄与し、ホストと病原体の両方の特定のメカニズムの特徴付けを可能にする。さらに、モデルは、免疫化および薬理学的介入を含む新規治療戦略のためにスクリーニングすることができる。このプロトコル?...

慢性炎症は、病理学的な組織の損傷およびヒトにおける多くの慢性疾患の統一特性の主要なドライバです。これらの疾患は、腫瘍性、自己免疫および慢性炎症性疾患1が含まれています。多くの慢性疾患の病因は依然として不明であるが、遺伝的素因および環境因子の導入の両方を含む、複雑で多因子性であると理解される。炎症のperpetuatorsはとらえどころのない残っていますが、免疫活性化の細胞および分子プロファイルは、病原体2に対する宿主応答において観察されるもののパターンとかなり重複する。 証拠が慢性炎症とその多様な臨床症状2,3の発症および進行中の微生物病原体の感染を暗示。病原体は、宿主の免疫系を破壊し、持続感染を確立することにより、直接、慢性炎症を誘導および維持することができます<sup&gt; 4。微生物の持続性の非存在下では、感染症、自己抗原分子擬態によりトリガ自己免疫反応は、免疫原性、それらをレンダリングする自己抗原、または以前にマスクされた宿主抗原を放出する損傷の変化による慢性炎症を沈殿させることができる。まれただし、特定の病原体は、特定の慢性疾患の普遍的な原因として同定されている。むしろ、利用可能なデータの大部分は、病原体は、遺伝的に感受性のホスト3における臨床症状および疾患転帰の広いスペクトルを有する慢性炎症を誘発するために異なるメカニズムを使用することを示唆している。したがって、特定の病原体が慢性炎症を誘導するメカニズムの詳細な理解は、主要な公衆衛生への影響だけでなく、多くの慢性疾患の治療および予防であってもよい。 慢性炎症の誘導および維持に貢献ホストと病原体の特定のメカニズムがありますがあまり理解されていない、病原体によって誘発される慢性炎症のモデル化における進歩は、これらのプロセスの理解を促進するために始めている。 P.歯周経口感染モデルは、ホストと病原ローカル（口頭骨の損失）で慢性炎症に貢献する具体的な仕組みや全身の部位（アテローム性動脈硬化症）5,6の分析、病原体によって誘発される慢性炎症のユニークな、十分に特徴付けられたマウスモデルである。 P.ジンジバリスは、人間の歯周病、組織7を支持歯の破壊を特徴とする感染主導の慢性炎症性疾患に関与するグラム陰性、嫌気性口腔病原体である。感染の初期部位における病理学に加えて、証拠が蓄積P.を暗示ジンジバリスは 、アテローム性動脈硬化症5を含む全身性疾患の発症および進行中の慢性inflammatioを特徴とする疾患を慢性炎症誘発動脈血管壁のnである。 Pと特定病原体フリーのマウスの経口感染ジンジバリスは、歯の破壊の結果は、歯槽骨8を支持することが局所的な炎症応答を誘導する。P.ジンジバリスは、病原体特異的血清抗体力価9の高レベルを開発するまでの42日感染後8およびマウス感染マウスの口から回収することができる。 - / -マウス（アポE - / - ）、P.経口感染アポリポタンパク質-Eを使用して、アテローム性動脈硬化症の確立されたマウスモデルにおいてジンジバリスは大動脈洞10と腕頭動脈11内炎症性プラーク沈着を駆動慢性炎症を誘導する。 Pの腕頭動脈内のプログレッシブ炎症歯周マウスは、生体内 MRI で使用して生きた動物でモニターすることができる感染した。組織学的には、Pから動脈病変歯周マウスは脂質accompa蓄積の増加を示し、感染した血管内皮の活性化、増加した免疫細胞浸潤、および炎症性メディエーター12の発現の上昇によって、防災科学技術研究所。ノックアウトマウスでのこのモデルの使用は、宿主シグナル伝達成分および炎症性メディエーターの役割、ならびに細胞P.を駆動特異的相互作用を解明している14 - 歯周は免疫病理12誘発 。また、定義された細菌の変異株を用いた実験では、重要なPを同定している歯周は、ローカルおよび全身の部位15で慢性炎症に貢献する要因を病原性。 この記事では、Pの評価のための方法論を詳述歯周は、ローカルおよび全身の部位での慢性炎症を誘発。私たちは、アミラソフトウェアを使用してマイクロCTによって歯槽骨喪失の分析のための詳細なプロトコルを提供する。さらに、当社は、プログレッシブでの評価のための生体内で生きている動物のMRI におけるシリアルの有用性を定義する腕頭動脈内のflammation。私たちは、動脈病変における炎症性プラークの可視化および定量化のための方法論が含まれ、それらの組織学的特徴づけを説明します。トランスジェニックマウスおよび定義された細菌の突然変異体の使用は、宿主および疾患の開始、進行および予後に関与する微生物因子の両方を識別するためのこのモデルは特に適している。さらに、モデルは、ワクチン接種および薬理学的介入を含む新規治療戦略のためにスクリーニングすることができる。

<table><tbody><tr><td>Amira analysis software</td><td>Visualization Sciences Group</td><td></td><td></td></tr><tr><td>Anaerobic chamber DW Scientific Model MG500&amp;nbsp;</td><td>Microbiology International</td><td></td><td></td></tr><tr><td>BHI&amp;nbsp;</td><td>Becton-Dickinson&amp;nbsp;</td><td>211059</td><td></td></tr><tr><td>Hemin&amp;nbsp;</td><td>Sigma-Aldrich&amp;nbsp;</td><td>51280-5G</td><td></td></tr><tr><td>Menadione (Vitamin K)</td><td>Sigma-Aldrich&amp;nbsp;&amp;nbsp;</td><td>M5625-25G</td><td></td></tr><tr><td>Yeast Extract</td><td>Becton-Dickinson&amp;nbsp;</td><td>212750</td><td></td></tr><tr><td>Carboxymethyl cellulose (medium viscocity)&amp;nbsp;</td><td>Sigma-Aldrich&amp;nbsp;</td><td>C-4888</td><td></td></tr><tr><td>Sulfamethoxazole and trimethoprim oral suspension 200 mg/40 mg per 5 ml</td><td>Hi-Tech Pharmacal</td><td>NDC 50383-823-16</td><td></td></tr><tr><td>&amp;mu;CT 40&amp;nbsp;</td><td>Scanco</td><td></td><td></td></tr><tr><td>HistoChoice Tissue Fixative</td><td>Sigma-Aldrich&amp;nbsp;</td><td>H2904</td><td></td></tr><tr><td>Sudan IV</td><td>Sigma-Aldrich&amp;nbsp;</td><td>S4261-25G</td><td></td></tr><tr><td>Vertical-bore 11.7T Avance spectrometer&amp;nbsp;</td><td>Bruker</td><td></td><td></td></tr><tr><td>Paravision</td><td>Paravision</td><td></td><td></td></tr><tr><td>ImageJ</td><td>NIH</td><td></td><td></td></tr><tr><td>Rat anti-mouse F4/80</td><td>Serotec</td><td>MCA497R</td><td></td></tr><tr><td>Rat anti-mouse TLR2</td><td>eBioscience</td><td>13-9021-80</td><td></td></tr><tr><td>Leica S4 dissecting scope</td><td>Leica</td><td></td><td></td></tr><tr><td>Microm HM 550 cryostat</td><td>Microm</td><td></td><td></td></tr></tbody></table>

a mouse model for pathogen-induced chronic inflammation at local and systemic sites

慢性炎症は、病理学的な組織の損傷及び腫瘍性、自己免疫および慢性炎症性疾患を含むヒトにおける多くの慢性疾患の統一特性の主要なドライバです。新たな証拠は、臨床症状の多種多様な慢性疾患の発症および進行中の病原体により誘導される慢性炎症を暗示。慢性疾患の複雑で多因子病因に、因果関係の証明および機構のリンクの確立のための実験を​​設計するヒトではほぼ不可能です。動物モデルを使用する利点は、特定の疾患の経過に影響を与える可能性の両方の遺伝的要因と環境要因を制御することができるということである。したがって、感染症の関連する動物モデルを設計する慢性炎症に寄与し、ホストおよび病原体特異的なメカニズムを特定するのに重要なステップである。 ここでは、病原体によって誘発される慢性inflaのマウスモデルを記述する口腔病原体ポルフィロモナス·ジンジバリス 、密接に人間の歯周病に関連する細菌による感染後の局所及び全身の部位でmmation。特定病原体フリーのマウスの経口感染が歯槽骨、歯周疾患の特徴を支える歯の破壊をもたらす局所的炎症応答を誘導する。アテローム性動脈硬化症の確立されたマウスモデル、P.による感染でジンジバリスは、血管内皮の活性化、増加した免疫細胞浸潤、および病変内の炎症性メディエータの発現の上昇を伴う大動脈洞および腕頭動脈内の炎症性プラーク沈着を加速させます。私たちは、局所および全身の部位での炎症の評価のための詳細な方法論。トランスジェニックマウスおよび定義された細菌の突然変異体の使用は、宿主および疾患の開始、進行および予後に関与する微生物因子の両方を識別するためのこのモデルは特に適している。 Additionallyは、モデルは、ワクチン接種および薬理学的介入を含む新規治療戦略のためにスクリーニングすることができる。

適切なマウスモデルおよび経口感染レジメン、P.を使用して歯周は （口腔）局所および全身の部位（動脈）（ 図1）で、慢性炎症や免疫病理を誘発する。 Pとマウスでは、経口感染ジンジバリスは、歯槽骨8を支持する歯の破壊を駆動する局所炎症応答を誘導する。P.歯周マウスは主にIgGアイソタイプ9の...

Watch this Scientific Journal Video about A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites at JoVE.com

A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites

動物モデルは、慢性炎症の発展に貢献宿主および病原体特異的なメカニズムを定義する上で非常に貴重なツールであることが分かっている。ここでは、ローカルおよび全身の部位での炎症の進行を評価するために、ヒト病原体ポルフィロモナス·ジンジバリスとディテールの方法論で経口感染のマウスモデルを記述する。

局所および全身所における病原体により誘導される慢性炎症のためのマウスモデル

Chronic inflammation is a major driver of pathological tissue damage and a unifying characteristic of many chronic diseases in humans including ...

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Immunology and Infection

17.5K ビュー.  Boston University School of Medicine. 動物モデルは、慢性炎症の発展に貢献宿主および病原体特異的なメカニズムを定義する上で非常に貴重なツールであることが分かっている。ここでは、ローカルおよび全身の部位での炎症の進行を評価するために、ヒト病原体ポルフィロモナス·ジンジバリスとディテールの方法論で経口感染のマウスモデルを記述する。 

ビデオ: A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites

The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis

This protocol outlines the steps required to produce a robust model of infectious disease and colitis, as well as the methods used to characterize Citrobacter rodentium infection in mice. C. rodentium is a gram negative, murine specific bacterial pathogen that is closely related to the clinically important human pathogens enteropathogenic E. coli and enterohemorrhagic E. coli. Upon infection with C. rodentium, immunocompetent mice suffer from modest and transient weight loss and diarrhea. Histologically, intestinal crypt elongation, immune cell infiltration, and goblet cell depletion are observed. Clearance of infection is achieved after 3 to 4 weeks. Measurement of intestinal epithelial barrier integrity, bacterial load, and histological damage at different time points after infection, allow the characterization of mouse strains susceptible to infection.
The virulence mechanisms by which bacterial pathogens colonize the intestinal tract of their hosts, as well as specific host responses that defend against such infections are poorly understood. Therefore the C. rodentium model of enteric bacterial infection serves as a valuable tool to aid in our understanding of these processes. Enteric bacteria have also been linked to Inflammatory Bowel Diseases (IBDs). It has been hypothesized that the maladaptive chronic inflammatory responses seen in IBD patients develop in genetically susceptible individuals following abnormal exposure of the intestinal mucosal immune system to enteric bacteria. Therefore, the study of models of infectious colitis offers significant potential for defining potentially pathogenic host responses to enteric bacteria. C. rodentium induced colitis is one such rare model that allows for the analysis of host responses to enteric bacteria, furthering our understanding of potential mechanisms of IBD pathogenesis; essential in the development of novel preventative and therapeutic treatments.

The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis

Citrobacter rodentium infection provides a valuable model to study enteric bacterial infections as well as host immune responses and colitis in mice. This protocol outlines the measurement of barrier integrity, pathogen load and histological damage allowing for the thorough characterization of pathogen and host contributions to murine infectious colitis.

ザ<em&gt;シトロrodentium</em&gt;マウスモデル：感染性大腸炎に勉強病原体とホスト貢献

This protocol  outlines the steps required to produce a robust model of infectious disease and  colitis, as well as the methods used to characterize ...

免疫・感染学

Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature

Neisseria meningitidis causes a severe, frequently fatal sepsis when it enters the human blood stream. Infection leads to extensive damage of the blood vessels resulting in vascular leak, the development of purpuric rashes and eventual tissue necrosis. Studying the pathogenesis of this infection was previously limited by the human specificity of the bacteria, which makes in vivo models difficult. In this protocol, we describe a humanized model for this infection in which human skin, containing dermal microvessels, is grafted onto immunocompromised mice. These vessels anastomose with the mouse circulation while maintaining their human characteristics. Once introduced into this model, N. meningitidis adhere exclusively to the human vessels, resulting in extensive vascular damage, inflammation and in some cases the development of purpuric rash. This protocol describes the grafting, infection and evaluation steps of this model in the context of N. meningitidis infection. The technique may be applied to numerous human specific pathogens that infect the blood stream.

Neisseria meningitidis is a human specific pathogen that infects blood vessels. In this protocol human microvessels are introduced into a mouse by grafting human skin onto immunocompromised mice. Bacteria adhere extensively to the human vessels, leading to vascular damage and development of the purpuric rash typically observed in human cases.

微小血管系を対象に細菌感染を研究するためのヒト化マウスモデル

Neisseria meningitidis causes a severe, frequently fatal sepsis when it enters the human blood stream. Infection leads to extensive damage of the blood ...

Chronic Salmonella Infected Mouse Model

The bacterial infected mouse model is a powerful model system for studying areas such as infection, inflammation, immunology, signal transduction, and tumorigenesis. Many researchers have taken advantage of the colitis induced by Salmonella typhimurium for the studies on the early phase of inflammation and infection. However, only few reports are on the chronic infection in vivo. Mice with Salmonella persistent existence in the gastrointestinal tract allow us to explore the long-term host-bacterial interaction, signal transduction, and tumorigenesis. We have established a chronic bacterial infected mouse model with Salmonella typhimurium colonization in the mouse intestine over 6 months. To use this system, it is necessary for the researcher to learn how to prepare the bacterial culture and gavage the animals. We detail a methodology for prepare bacterial culture and gavage mice. We also show how to detect the Salmonella persistence in the gastrointestinal tract. Overall, this protocol will aid researchers using the bacterial infected mouse model to address fundamentally important biological and microbiological questions.

Chronic Salmonella Infected Mouse Model

Establish a chronic bacterial infected mouse model with persistent Salmonella typhimurium colonization in intestine for 27 weeks.

慢性サルモネラ感染マウスモデル

The bacterial infected mouse model is a powerful model system for studying areas such as infection, inflammation, immunology, signal transduction, and ...

生物学

Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues

Multiple sclerosis is presumed to be an inflammatory autoimmune disease, which is characterized by lesion formation in the central nervous system (CNS) resulting in cognitive and motor impairment. Experimental autoimmune encephalomyelitis (EAE) is a useful animal model of MS, because it is also characterized by lesion formation in the CNS, motor impairment and is also driven by autoimmune and inflammatory reactions. One of the EAE models is induced with a peptide derived from the myelin oligodendrocyte protein (MOG)35-55 in mice. The EAE mice develop a progressive disease course. This course is divided into three phases: the preclinical phase (day 0 - 9), the disease onset (day 10 - 11) and the acute phase (day 12 - 14). MS and EAE are induced by autoreactive T cells that infiltrate the CNS. These T cells secrete chemokines and cytokines which lead to the recruitment of further immune cells. Therefore, the immune cell distribution in the spinal cord during the three disease phases was investigated. To highlight the time point of the disease at which the activation/proliferation/accumulation of T cells, B cells and monocytes starts, the immune cell distribution in lymph nodes, spleen and blood was also assessed. Furthermore, the levels of several cytokines (IL-1&#946;, IL-6, IL-23, TNF&#945;, IFN&#947;) in the three disease phases were determined, to gain insight into the inflammatory processes of the disease. In conclusion, the data provide an overview of the functional profile of immune cells during EAE pathology.

This manuscript describes the methods for induction and scoring of the experimental autoimmune encephalomyelitis (EAE) model, together with the assessment of immune cell distribution and mRNA cytokine levels in lymph nodes, spleen, blood and spinal cord using flow cytometry and quantitative PCR, respectively, at various disease phases.

マウスおよび種々の組織における免疫細胞の疾患に依存する分布の評価における実験的自己免疫性脳脊髄炎の誘導

Multiple sclerosis is presumed to be an inflammatory autoimmune disease, which is characterized by lesion formation in the central nervous system (CNS) ...

An IL-8 Transiently Transgenized Mouse Model for the In Vivo Long-term Monitoring of Inflammatory Responses

Airway inflammation is often associated with bacterial infections and represents a major determinant of lung disease. The in vivo determination of the pro-inflammatory capabilities of various factors is challenging and requires terminal procedures, such as bronchoalveolar lavage and the removal of lungs for in situ analysis, precluding longitudinal visualization in the same mouse. Here, lung inflammation is induced through the intratracheal instillation of Pseudomonas aeruginosa culture supernatant (SN) in transiently transgenized mice expressing the luciferase reporter gene under the control of a heterologous IL-8 bovine promoter. Luciferase expression in the lung is monitored by in vivo bioluminescent image (BLI) analysis over a 2.5- to 48-h timeframe following the instillation. The procedure can be repeated multiple times within 2 - 3 months, thus permitting the evaluation of the inflammatory response in the same mice without the need to terminate the animals. This approach permits the monitoring of pro- and anti-inflammatory factors acting in the lung in real time and appears suitable for functional and pharmacological studies.

An IL-8 Transiently Transgenized Mouse Model for the In Vivo Long-term Monitoring of Inflammatory Responses

The method described here allows for the visualization of IL-8 promoter-dependent inflammation activation in the lungs of mice through non-invasive bioluminescence imaging (BLI). The same animal can be subjected to BLI multiple times for up to two months from the time of delivery of the luciferase reporter construct.

IL-8トランジェントトランスジェニックマウスモデル<em&gt;インビボ</em&gt;炎症反応の長期モニタリング

Airway inflammation is often associated with bacterial infections and represents a major determinant of lung disease. The in vivo determination of the ...

The bm12 Inducible Model of Systemic Lupus Erythematosus (SLE) in C57BL/6 Mice

Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical and immunological manifestations. Several spontaneous and inducible animal models mirror common components of human disease, including the bm12 transfer model. Upon transfer of bm12 splenocytes or purified CD4 T cells, C57BL/6 mice rapidly develop large frequencies of T follicular helper cells (Tfh), germinal center (GC) B cells, and plasma cells followed by high levels of circulating anti-nuclear antibodies. Since this model utilizes mice on a pure C57BL/6 background, researchers can quickly and easily study disease progression in transgenic or knockout mouse strains in a relatively short period of time. Here we describe protocols for the induction of the model and the quantitation Tfh, GC B cells, and plasma cells by multi-color flow cytometry. Importantly, these protocols can also be used to characterize disease in most mouse models of SLE and identify Tfh, GC B cells, and plasma cells in other disease models.

The bm12 Inducible Model of Systemic Lupus Erythematosus SLE in C57BL/6 Mice

The transfer of bm12 lymphocytes into a C57BL/6 recipient is an established model of systemic lupus erythematosus. Here we describe how to initiate disease using this model and how to characterize T follicular helper cells, germinal center B cells and plasma cells by flow cytometry.

C57BL / 6マウスにおける全身性エリテマトーデス（SLE）のBM12誘導モデル

Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical and immunological manifestations. Several spontaneous and inducible ...

医学

Bioluminescence and Near-infrared Imaging of Optic Neuritis and Brain Inflammation in the EAE Model of Multiple Sclerosis in Mice

Experimental autoimmune encephalomyelitis (EAE) in SJL/J mice is a model for relapsing-remitting multiple sclerosis (RRMS). Clinical EAE scores describing motor function deficits are basic readouts of the immune-mediated inflammation of the spinal cord. However, scores and body weight do not allow for an in vivo assessment of brain inflammation and optic neuritis. The latter is an early and frequent manifestation in about 2/3 of MS patients. Here, we show methods for bioluminescence and near-infrared live imaging to assess EAE evoked optic neuritis, brain inflammation, and blood-brain barrier (BBB) disruption in living mice using an in vivo imaging system. A bioluminescent substrate activated by oxidases primarily showed optic neuritis. The signal was specific and allowed the visualization of medication effects and disease time courses, which paralleled the clinical scores. Pegylated fluorescent nanoparticles that remained within the vasculature for extended periods of time were used to assess the BBB integrity. Near-infrared imaging revealed a BBB leak at the peak of the disease. The signal was the strongest around the eyes. A near-infrared substrate for matrix metalloproteinases was used to assess EAE-evoked inflammation. Auto-fluorescence interfered with the signal, requiring spectral unmixing for quantification. Overall, bioluminescence imaging was a reliable method to assess EAE-associated optic neuritis and medication effects and was superior to the near-infrared techniques in terms of signal specificity, robustness, ease of quantification, and cost.

We show a technique for in vivo live bioluminescence and near-infrared imaging of optic neuritis and encephalitis in the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis in SJL/J mice.

マウスにおける多発性硬化症のEAEモデルにおける視神経炎と脳炎症の生物発光と近赤外イメージング

Experimental autoimmune encephalomyelitis (EAE) in SJL/J mice is a model for relapsing-remitting multiple sclerosis (RRMS). Clinical EAE scores describing ...

A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection

Staphylococcus aureus (S. aureus)&#160;infections, including methicillin resistant stains, are an enormous burden on the healthcare system. With incidence rates of S. aureus infection climbing annually, there is a demand for additional research in its&#160;pathogenicity. Animal models of infectious disease advance our understanding of the host-pathogen response and lead to the development of effective therapeutics. Neutrophils play a primary role in the innate immune response that controls S. aureus infections by forming an abscess to wall off the infection and facilitate bacterial clearance; the number of neutrophils that infiltrate an S. aureus skin infection often correlates with disease outcome. LysM-EGFP mice, which possess the enhanced green fluorescent protein (EGFP) inserted in the Lysozyme M (LysM) promoter region (expressed primarily by neutrophils), when used in conjunction with in vivo whole animal fluorescence imaging (FLI) provide&#160;a means of quantifying neutrophil emigration noninvasively and longitudinally into wounded skin. When combined with a bioluminescent S. aureus strain and sequential in vivo whole animal bioluminescent imaging (BLI), it is possible to longitudinally monitor both the neutrophil recruitment dynamics and in vivo bacterial burden at the site of infection in anesthetized mice from onset of infection to resolution or death. Mice are more resistant to a number of virulence factors produced by S. aureus that facilitate effective colonization and infection in humans. Immunodeficient mice provide a more sensitive animal model to examine persistent S. aureus infections and the ability of therapeutics to boost innate immune responses. Herein, we characterize responses in LysM-EGFP mice that have been bred to MyD88-deficient mice (LysM-EGFP&#215;MyD88-/- mice) along with wild-type LysM-EGFP mice to investigate S. aureus skin wound infection. Multispectral simultaneous detection enabled study of neutrophil recruitment dynamics by using in vivo FLI, bacterial burden by using in vivo BLI, and wound healing longitudinally and noninvasively over time.

A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection

An approach is described for real-time detection of the innate immune response to cutaneous wounding and Staphylococcus aureus infection of mice. By comparing LysM-EGFP mice (which possess fluorescent neutrophils) with a LysM-EGFP crossbred immunodeficient mouse strain, we advance our understanding of infection and the development of approaches to combat infection.

マウスのモデルを評価する生得の免疫反応黄色ブドウ球菌感染症

Staphylococcus aureus (S. aureus)&#160;infections, including methicillin resistant stains, are an enormous burden on the healthcare system. With incidence ...

Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses

This protocol describes a footpad inoculation model used to study the initiation and development of neuroinflammatory responses during alphaherpesvirus infection in mice. As alphaherpesviruses are main invaders of the peripheral nervous system (PNS), this model is suitable to characterize the kinetics of viral replication, its spread from the PNS to CNS, and associated neuroinflammatory responses. The footpad inoculation model allows virus particles to spread from a primary infection site in the footpad epidermis to sensory and sympathetic nerve fibers that innervate the epidermis, sweat glands, and dermis. The infection spreads via the sciatic nerve to the dorsal root ganglia (DRG) and ultimately through the spinal cord to the brain. Here, a mouse footpad is inoculated with pseudorabies virus (PRV), an alphaherpesvirus closely related to herpes simplex virus (HSV) and varicella-zoster virus (VZV). This model demonstrates that PRV infection induces severe inflammation, characterized by neutrophil infiltration in the footpad and DRG. High concentrations of inflammatory cytokines are subsequently detected in homogenized tissues by ELISA. In addition, a strong correlation is observed between PRV gene and protein expression (via qPCR and IF staining) in DRG and the production of pro-inflammatory cytokines. Therefore, the footpad inoculation model provides a better understanding of the processes underlying alphaherpesvirus-induced neuropathies and may lead to the development of innovative therapeutic strategies. In addition, the model can guide research on peripheral neuropathies, such as multiple sclerosis and associated viral-induced damage to the PNS. Ultimately, it can serve as a cost-effective in vivo tool for drug development.

The footpad inoculation model is a valuable tool for characterizing viral-induced neuroinflammatory responses in vivo. In particular, it provides a clear assessment of viral kinetics and associated immunopathological processes initiated in the peripheral nervous system.

ウイルス誘導神経炎症反応を研究するマウスフットパッド接種モデル

This protocol describes a footpad inoculation model used to study the initiation and development of neuroinflammatory responses during alphaherpesvirus ...

A Mouse Model for the Transition of Streptococcus pneumoniae from Colonizer to Pathogen upon Viral Co-Infection Recapitulates Age-Exacerbated Illness

Streptococcus pneumoniae (pneumococcus) is an asymptomatic colonizer of the nasopharynx in most individuals but can progress to a pulmonary and systemic pathogen upon influenza A virus (IAV) infection. Advanced age enhances host susceptibility to secondary pneumococcal pneumonia and is associated with worsened disease outcomes. The host factors driving those processes are not well defined, in part due to a lack of animal models that reproduce the transition from asymptomatic colonization to severe clinical disease. 
This paper describes a novel mouse model that recreates the transition of pneumococci from asymptomatic carriage to disease upon viral infection. In this model, mice are first intranasally inoculated with biofilm-grown pneumococci to establish asymptomatic carriage, followed by IAV infection of both the nasopharynx and lungs. This results in bacterial dissemination to the lungs, pulmonary inflammation, and obvious signs of illness that can progress to lethality. The degree of disease is dependent on the bacterial strain and host factors. 
Importantly, this model reproduces the susceptibility of aging, because compared to young mice, old mice display more severe clinical illness and succumb to disease more frequently. By separating carriage and disease into distinct steps and providing the opportunity to analyze the genetic variants of both the pathogen and the host, this S. pneumoniae/IAV co-infection model permits the detailed examination of the interactions of an important pathobiont with the host at different phases of disease progression. This model can also serve as an important tool for identifying potential therapeutic targets against secondary pneumococcal pneumonia in susceptible hosts.

A Mouse Model for the Transition of Streptococcus pneumoniae from Colonizer to Pathogen upon Viral Co-Infection Recapitulates Age-Exacerbated Illness

This paper describes a novel mouse model for the transition of pneumococcus from an asymptomatic colonizer to a disease-causing pathogen during viral infection. This model can be readily adapted to study polymicrobial and host-pathogen interactions during the different phases of disease progression and across various hosts.

肺炎 連鎖 球菌のウイルス重感染によるコロニー形成者から病原体への移行に関するマウスモデルが加齢増悪疾患を再現

Streptococcus pneumoniae (pneumococcus) is an asymptomatic colonizer of the nasopharynx in most individuals but can progress to a pulmonary and systemic ...

局所および全身所における病原体により誘導される慢性炎症のためのマウスモデル

要約

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この動画の章

ザ

微小血管系を対象に細菌感染を研究するためのヒト化マウスモデル

慢性サルモネラ感染マウスモデル

マウスおよび種々の組織における免疫細胞の疾患に依存する分布の評価における実験的自己免疫性脳脊髄炎の誘導

IL-8トランジェントトランスジェニックマウスモデル

C57BL / 6マウスにおける全身性エリテマトーデス（SLE）のBM12誘導モデル

マウスにおける多発性硬化症のEAEモデルにおける視神経炎と脳炎症の生物発光と近赤外イメージング

マウスのモデルを評価する生得の免疫反応黄色ブドウ球菌感染症

ウイルス誘導神経炎症反応を研究するマウスフットパッド接種モデル

肺炎連鎖球菌のウイルス重感染によるコロニー形成者から病原体への移行に関するマウスモデルが加齢増悪疾患を再現

局所および全身所における病原体により誘導される慢性炎症のためのマウスモデル

要約

さらに動画を探す

この動画の章

ザ

微小血管系を対象に細菌感染を研究するためのヒト化マウスモデル

慢性サルモネラ感染マウスモデル

マウスおよび種々の組織における免疫細胞の疾患に依存する分布の評価における実験的自己免疫性脳脊髄炎の誘導

IL-8トランジェントトランスジェニックマウスモデル

C57BL / 6マウスにおける全身性エリテマトーデス（SLE）のBM12誘導モデル

マウスにおける多発性硬化症のEAEモデルにおける視神経炎と脳炎症の生物発光と近赤外イメージング

マウスのモデルを評価する生得の免疫反応黄色ブドウ球菌感染症

ウイルス誘導神経炎症反応を研究するマウスフットパッド接種モデル

肺炎 連鎖 球菌のウイルス重感染によるコロニー形成者から病原体への移行に関するマウスモデルが加齢増悪疾患を再現

肺炎連鎖球菌のウイルス重感染によるコロニー形成者から病原体への移行に関するマウスモデルが加齢増悪疾患を再現