Aging Dampens the Intestinal Innate Immune Response during Severe Clostridioides difficile Infection and Is Associated with Altered Cytokine Levels and Granulocyte Mobilization.

Autor:	Abernathy-Close L; Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Dieterle MG; Medical Scientist Training Program, University of Michigan, Ann Arbor, Michigan, USA.; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA., Vendrov KC; Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Bergin IL; Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Rao K; Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Young VB; Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA youngvi@umich.edu.; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2020 May 20; Vol. 88 (6). Date of Electronic Publication: 2020 May 20 (Print Publication: 2020).
DOI:	10.1128/IAI.00960-19
Abstrakt:	Clostridioides (formerly Clostridium ) difficile is the most common cause of hospital-acquired infection, and advanced age is a risk factor for C. difficile infection. Disruption of the intestinal microbiota and immune responses contribute to host susceptibility and severity of C. difficile infection. However, the specific impact of aging on immune responses during C. difficile infection remains to be well described. This study explores the effect of age on cellular and cytokine immune responses during C. difficile infection. Young mice (2 to 3 months old) and aged mice (22 to 28 months old) were rendered susceptible to C. difficile infection with the antibiotic cefoperazone and then infected with C. difficile strains with varied disease-causing potentials. We observe that the host age and the infecting C. difficile strain influenced the severity of disease associated with infection. Tissue-specific CD45 + immune cell responses occurred at the time of peak disease severity in the ceca and colons of all mice infected with a high-virulence strain of C. difficile ; however, significant deficits in intestinal neutrophils and eosinophils were detected in aged mice, with a corresponding decrease in circulating CXCL1, an important neutrophil recruiter and activator. Interestingly, this lack of intestinal granulocyte response in aged mice during severe C. difficile infection was accompanied by a simultaneous increase in circulating white blood cells, granulocytes, and interleukin 17A (IL-17A). These findings demonstrate that age-related alterations in neutrophils and eosinophils and systemic cytokine and chemokine responses are associated with severe C. difficile infection and support a key role for intestinal eosinophils in mitigating C. difficile -mediated disease severity. (Copyright © 2020 American Society for Microbiology.)
Databáze:	MEDLINE
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