AUTHOR=Nascimento Danielle de Oliveira , Vieira-de-Abreu Adriana , Arcanjo Angélica F. , Bozza Patricia Torres , Zimmerman Guy A. , Castro-Faria-Neto Hugo Caire 

TITLE=Integrin αDβ2 (CD11d/CD18) Modulates Leukocyte Accumulation, Pathogen Clearance, and Pyroptosis in Experimental Salmonella Typhimurium Infection

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01128

DOI=10.3389/fimmu.2018.01128

ISSN=1664-3224

ABSTRACT=<p>β<sub>2</sub> integrins are critical in host defense responses to invading pathogens and inflammation. Previously, we reported that genetic deficiency of integrin α<sub>D</sub>β<sub>2</sub> in mice altered outcomes in experimental systemic infections including accelerated mortality in animals infected with <italic>Salmonella enterica</italic> serovar Typhimurium. Here, we show that deficiency of α<sub>D</sub>β<sub>2</sub> results in impaired accumulation of leukocytes in response to peritoneal infection by <italic>S</italic>. Typhimurium, impaired pathogen clearance <italic>in vivo</italic>, defective bacterial elimination by cultured peritoneal macrophages, and enhanced pyroptosis, a cell death process triggered by <italic>Salmonella</italic>. <italic>Salmonella</italic>-infected animals deficient in α<sub>D</sub>β<sub>2</sub> had increased levels of peritoneal cytokines in addition to other markers of pyroptosis, which may contribute to inflammatory injury and increased mortality in the context of impaired bacterial killing. These observations indicate important contributions of leukocyte integrins to the host response in experimental <italic>Salmonella</italic> infection and reveal previous activities of α<sub>D</sub>β<sub>2</sub> in bacterial infection.</p>