Autophagy Limits Inflammasome During Chlamydia pneumoniae Infection

In this study we found blocking autophagy led to increased CP growth in both macrophages and mouse embryonic fibroblasts. In vivo, loss of the autophagy elongation component ATG16L1 specifically in myeloid cells led to increased mortality in response to CP infection, characterized by greater numbers of neutrophils and dendritic cells, but no change in the CP burden in the lungs. This was accompanied by an increase in inflammasome-active macrophages and IL-1β production. While induction of autophagy in macrophages led to reduced CP growth in vitro, in vivo treatment with rapamycin led to increased mortality of infected mice, likely due to initial impairment in IL-1β production resulting in increased bacterial load. Materials and Methods Mice and Cell Lines C57BL/6 (wild-type [WT]) mice were purchased from Jackson Labs (Bar Harbor, ME) and then bred in the Cedars-Sinai Medical Center Comparative Medicine facility. Atg16l1fl/fl Lysmcre mice were obtained from Dr. David Shih, Cedars-Sinai medical Center (26). Atg16l1fl/fl mice were used as littermate controls. Eight- to ten-weeks-old female mice were used in all experiments in this study. WT, Atg16l1+/−, and Atg5−/− mouse embryonic fibroblasts (MEF)s were obtained from Dr. Jae Jung (University of Southern California) (27) and grown in DMEM media containing 10% FBS. In some cases, 1 μg/ml cycloheximide (Sigma Aldrich, St. Louis MO), MEM amino acids (Sigma Aldrich, St. Louis MO), or Na-pyruvate (Si...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Source: Revista de Saude Publica - Category: International Medicine & Public Health Source Type: research
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Source: Revista de Saude Publica - Category: International Medicine & Public Health Source Type: research
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Source: Revista de Saude Publica - Category: International Medicine & Public Health Source Type: research
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Source: SafetyLit - Category: International Medicine & Public Health Tags: Jurisprudence, Laws, Legislation, Policies, Rules Source Type: news
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Source: SafetyLit - Category: International Medicine & Public Health Tags: Age: Adolescents Source Type: news
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Source: SafetyLit - Category: International Medicine & Public Health Tags: Age: Adolescents Source Type: news
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Source: SafetyLit - Category: International Medicine & Public Health Tags: Age: Adolescents Source Type: news
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Source: SafetyLit - Category: International Medicine & Public Health Tags: Jurisprudence, Laws, Legislation, Policies, Rules Source Type: news
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Source: SafetyLit - Category: International Medicine & Public Health Tags: Jurisprudence, Laws, Legislation, Policies, Rules Source Type: news
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Source: SafetyLit - Category: International Medicine & Public Health Tags: Jurisprudence, Laws, Legislation, Policies, Rules Source Type: news
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