Role of inflammatory monocytes in immunity and host defense against Salmonella

炎症单核细胞在沙门氏菌免疫和宿主防御中的作用

• 批准号: 10689679
• 负责人: Adrianus Wilhelmus Maria van der Velden
• 金额: $ 55.58万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-03 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10689679
• 关键词: Address; Antigen Presentation; Bacteremia; Bacteria; Bone Marrow; CC chemokine receptor 2; Cells; Cessation of life; Clinical; Colitis; Complex; Dendritic Cells; Exhibits; Gastroenteritis; Generations; Goals; Granuloma; Growth; Health; Host Defense; Human; Immune; Immune response; Immunity; Immunosuppression; In Vitro; Infection; Infiltration; Inflammatory; Innate Immune Response; Knowledge; Laboratories; Ligands; Macrophage; Maintenance; Malignant Neoplasms; Manuscripts; Mononuclear; Morbidity - disease rate; Mus; Myeloid Cells; Myeloid-derived suppressor cells; NOS2A gene; Nitrates; Outcome; Pathogenesis; Pathologic; Pathology; Peripheral; Play; Predisposition; Preparation; Property; Publishing; Research; Role; Salmonella; Salmonella enterica; Salmonella infections; Salmonella typhimurium; Severities; Syndrome; System; T cell response; T-Cell Proliferation; T-Lymphocyte; Testing; Tissues; Typhoid Fever; Work; adaptive immune response; beta-Chemokines; cell type; expectation; gut inflammation; inflammatory modulation; innovation; insight; monocyte; mortality; mouse model; pathogenic bacteria; progenitor; recruit

PROJECT SUMMARY Inflammatory monocytes are innate immune cells that play a key role in immunity and host defense. They originate from progenitors in bone marrow and, under certain pathological conditions, can be recruited from bone marrow into tissues. Inflammatory monocytes resemble mononuclear myeloid-derived suppressor cells, which have been associated with immunosuppression in cancer and, more recently infection; yet their role in host immune responses to bacterial triggers is not well understood. To address this knowledge gap, we have been investigating the role of inflammatory monocytes in the host immune response to Salmonella, which are pathogenic bacteria that cause significant morbidity and mortality in humans worldwide. We have published that inflammatory monocytes purified from tissues of mice infected with Salmonella exhibit both protective and immunosuppressive properties that may influence the outcome of the infection. Furthermore, we have published that inflammatory monocytes provide a niche for Salmonella expansion in the lumen of the inflamed intestine. Recent work from our laboratory described in this application has indicated that inflammatory monocytes play an essential role in both early and late control of persistent Salmonella infection. Collectively, these published and unpublished findings establish that inflammatory monocytes play a key role in the host immune response to Salmonella. The objective of this application is to define how inflammatory monocytes modulate host interactions with Salmonella, a high impact topic important for understanding the role of inflammatory monocytes in immunity and host defense. Our central hypothesis is that inflammatory monocytes play a key role not only in the induced innate immune response to Salmonella, but also in directing the course of the adaptive immune response to Salmonella. To test various aspects of our central hypothesis and accomplish our objective, we will 1) define how inflammatory monocytes contribute to the pathogenesis of Salmonella-induced colitis and 2) define how inflammatory monocytes help control persistent Salmonella infection. Conceptual advances resulting from the proposed research are expected to provide new, fundamental insights into the role of inflammatory monocytes in immunity and host defense, and thus will have a strong and sustained influence on the field.

项目总结

项目成果

CCR2+ Inflammatory Monocytes Are Recruited to Yersinia pseudotuberculosis Pyogranulomas and Dictate Adaptive Responses at the Expense of Innate Immunity during Oral Infection.

CCR2 炎症单核细胞被招募到假结核耶尔森菌脓性肉芽肿中，并在口腔感染期间以牺牲先天免疫为代价来指示适应性反应。

• DOI: 10.1128/iai.00782-17
• 发表时间: 2018
• 期刊: Infection and immunity
• 影响因子: 3.1
• 作者: Zhang,Yue;Khairallah,Camille;Sheridan,BrianS;vanderVelden,AdrianusWM;Bliska,JamesB
• 通讯作者: Bliska,JamesB

A blend of broadly-reactive and pathogen-selected Vγ4 Vδ1 T cell receptors confer broad bacterial reactivity of resident memory γδ T cells.

广泛反应和病原体选择的Vγ4Vδ1T细胞受体的混合物赋予了居民记忆γδT细胞的广泛细菌反应性。

• DOI: 10.1038/s41385-021-00447-x
• 发表时间: 2022-01
• 期刊: Mucosal immunology
• 影响因子: 8
• 作者: Khairallah C;Bettke JA;Gorbatsevych O;Qiu Z;Zhang Y;Cho K;Kim KS;Chu TH;Imperato JN;Hatano S;Romanov G;Yoshikai Y;Puddington L;Surh CD;Bliska JB;van der Velden AWM;Sheridan BS
• 通讯作者: Sheridan BS