Project description:Old C57BL/6 mice cannot mount an effective innate immune response We used mouse microarrays to detail the molecular profile of the events that occur following infection
Project description:The elderly have increased morbidity and mortality following sepsis; however, the cause(s) remains unclear. We hypothesized that these poor outcomes are due in part to defects in innate immunity, rather than to an exaggerated early inflammatory response. Young (6-12 wk) or aged (20-24 mo) mice underwent polymicrobial sepsis, and subsequently, the aged mice had increased mortality and defective peritoneal bacterial clearance compared with young mice. No differences were found in the magnitude of the plasma cytokine responses. Although septic aged mice displayed equivalent or increased numbers of circulating, splenic, and bone marrow myeloid cells, some of these cells exhibited decreased phagocytosis, reactive oxygen species production, and chemotaxis. Blood leukocyte gene expression was less altered in aged versus young mice 1 d after sepsis. Aged mice had a relative inability to upregulate gene expression of pathways related to neutrophil-mediated protective immunity, chemokine/chemokine receptor binding, and responses to exogenous molecules. Expression of most MHC genes remained more downregulated in aged mice at day 3. Despite their increased myeloid response to sepsis, the increased susceptibility of aged mice to sepsis appears not to be due to an exaggerated inflammatory response, but rather, a failure to mount an effective innate immune response.
Project description:Innate immunity is fundamental to recognition and clearance of bacterial infection. The relevant cells and molecules that orchestrate an effective response, however, remain incompletely understood. Here we describe a previously unknown population of B cells, which we have named innate response activator (IRA) B cells that recognize bacteria directly through TLR-4-MyD88 and protect against polymicrobial sepsis. IRA-B cells have a unique IgM high CD23 low CD43 + CD93+ GM-CSF+ signature, develop and diverge from B1a B cells, require BAFFR, and adhere to tissue via VLA-4 and LFA-1. B cell subsets are sorted from the spleen and peritoneum of C57BL/6 mice that were given intraperitoneal injections of LPS once daily for four days.
Project description:Innate immunity is fundamental to recognition and clearance of bacterial infection. The relevant cells and molecules that orchestrate an effective response, however, remain incompletely understood. Here we describe a previously unknown population of B cells, which we have named innate response activator (IRA) B cells that recognize bacteria directly through TLR-4-MyD88 and protect against polymicrobial sepsis. IRA-B cells have a unique IgM high CD23 low CD43 + CD93+ GM-CSF+ signature, develop and diverge from B1a B cells, require BAFFR, and adhere to tissue via VLA-4 and LFA-1.