IL-1α and Complement Cooperate in Triggering Local Neutrophilic Inflammation in Response to Adenovirus and Eliminating Virus-Containing Cells

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Adenovirus (Ad) induces a potent activation of pro-inflammatory cytokines and chemokines upon interaction with tissue macrophages in vivo. However, critical factors affecting cellular inflammatory responses to Ad and their functional significance remain unclear. Here we show that in the model of disseminated infection, intravenous Ad administration leads to a rapid release of pro-inflammatory Ly-6G+7/4+ leukocytes (PMNs) from the bone marrow into the blood. PMNs enter into peripheral tissues and, in the case of spleen, are accumulated in proximity to the virus-containing MARCO+ macrophages within the splenic marginal zone (MZ). Mechanistic dissection of molecular queues that guide PMN migration reveals that CXCL1 and CXCL2 chemokines are only partially responsible for CXCR2-dependent PMN recruitment into the splenic MZ. We further found that complement cooperates with IL-1α-IL-1RI-CXCR2 signaling pathways in recruitment of PMNs to the splenic MZ, which results in elimination of virus-containing MARCO+ macrophages from the spleen. Administration of complement-blocking CR2-Crry or CR2-fH proteins into IL-1α-deficient, but not wild-type, mice prevents PMN accumulation in the splenic MZ and elimination of virus-containing macrophages from the spleen. Our study defines the functional significance of molecular and cellular host defense mechanisms that cooperate in eliminating virus-containing cells in the model of acute disseminated Ad infection.

Vyšlo v časopise: IL-1α and Complement Cooperate in Triggering Local Neutrophilic Inflammation in Response to Adenovirus and Eliminating Virus-Containing Cells. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004035
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004035

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