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Immunol."],"abstract":"<jats:p>Intra-abdominal infection (peritonitis) is a leading cause of severe disease in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8\/A9 (calprotectin) is an antimicrobial and pro-inflammatory protein complex used as a biomarker for diagnosis of numerous inflammatory disorders. Here we describe the role of S100A8\/A9 in inflammatory collateral tissue damage (ICTD). Using a mouse model of disseminated intra-abdominal candidiasis (IAC) in wild-type and S100A8\/A9-deficient mice in the presence or absence of S100A9 inhibitor paquinimod, the role of S100A8\/A9 during ICTD and fungal clearance were investigated. S100A8\/A9-deficient mice developed less ICTD than wild-type mice. Restoration of S100A8\/A9 in knockout mice by injection of recombinant protein resulted in increased ICTD and fungal clearance comparable to wild-type levels. Treatment with paquinimod abolished ICTD and S100A9-deficient mice showed increased survival compared to wild-type littermates. The data indicates that S100A8\/A9 controls ICTD levels and antimicrobial activity during IAC and that targeting of S100A8\/A9 could serve as promising adjunct therapy against this challenging disease.<\/jats:p>","DOI":"10.3389\/fimmu.2021.553911","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T07:41:56Z","timestamp":1614325316000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Immune Resolution Dilemma: Host Antimicrobial Factor S100A8\/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis"],"prefix":"10.3389","volume":"12","author":[{"given":"Madhu","family":"Shankar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Uwamahoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emelie","family":"Backman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Holmberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Joanna","family":"Niemiec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Vogl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin 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