Monocytes represent one source of bacterial shielding from antibiotics following influenza virus infection

Karl J. Fischer, Vijaya Kumar Yajjala, Shruti Bansal, Christopher Bauer, Ruiling Chen, Keer Sun

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Abstract

Methicillin-resistant Staphylococcus aureus has emerged as a significant contributor to morbidity and mortality associated with influenza infection. In this study, we show in a mouse model that preceding influenza infection promotes S. aureus resistance to killing by antibiotics. This resistance coincides with influenza-induced accumulation of inflammatory monocytes in the lung. CCR type 2 (CCR2) is responsible for pulmonary monocyte recruitment after influenza infection. We found that antibiotic-treated Ccr2-deficient (Ccr2 -/- ) mice exhibit significantly improved bacterial control and survival from influenza and methicillinresistant S. aureus coinfection, despite a delay in viral clearance. Mechanistically, our results from in vivo studies indicate that influenza-induced monocytes serve as reservoirs for intracellular S. aureus survival, thereby promoting bacterial resistance to antibiotic treatment. Blocking CCR2 with a small molecular inhibitor (PF-04178903), in conjunction with antibiotic treatment, enhanced lung bacterial clearance and significantly improved animal survival. Collectively, our study demonstrates that inflammatory monocytes constitute an important and hitherto underappreciated mechanism of the conflicting immune requirements for viral and bacterial clearance by hosts, which subsequently leads to exacerbated outcomes of influenza and S. aureus coinfection.

Original languageEnglish (US)
Pages (from-to)2027-2034
Number of pages8
JournalJournal of Immunology
Volume202
Issue number7
DOIs
StatePublished - Jan 1 2019

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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