CXCL9 Contributes to Antimicrobial Protection of the Gut during Infection Independent of Chemokine-Receptor Signaling

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Host defense peptides are an essential part of the innate immune response to pathogens, particularly at mucosal surfaces. Some chemokines, previously known for their ability to recruit immune cells to a site of inflammation, have been identified to have direct antimicrobial activity in vitro against a variety of pathogens. Despite this, it was unknown whether chemokines play a role in protecting the gut mucosa against enteric pathogens, independent of their immunological receptors. Using a mouse model of enteric pathogen infection with both wild type mice and genetic knockouts, we showed that the chemokine CXCL9 has direct antimicrobial activity against pathogen infection. This antimicrobial activity prevented the invasion of bacteria into intestinal crypts, thus protecting the host from immunopathology. Neutralization of this CXCL9-dependent antimicrobial activity increased host susceptibility to infection, leading to bacterial penetration into intestinal crypts and increased tissue pathology. These data support the importance of a receptor-independent role for chemokines in host defense at mucosal surfaces and may offer alternative treatment strategies for infections, particularly in regards to organisms that are resistant to conventional antibiotics.

Vyšlo v časopise: CXCL9 Contributes to Antimicrobial Protection of the Gut during Infection Independent of Chemokine-Receptor Signaling. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004648
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004648

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