IL-1 signaling prevents alveolar macrophage depletion during influenza and streptococcus pneumoniae coinfection

Shruti Bansal, Vijaya Kumar Yajjala, Christopher Bauer, Keer Sun

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Influenza and bacterial coinfection is a significant cause of hospitalization and death in humans during influenza epidemics and pandemics. However, the fundamental protective and pathogenic mechanisms involved in this complex virus–host–bacterium interaction remain incompletely understood. In this study, we have developed mild to lethal influenza and Streptococcus pneumoniae coinfection models for comparative analyses of disease pathogenesis. Specifically, wild-type and IL-1R type 1–deficient (Il1r1 2 / 2 ) mice were infected with influenza virus and then superchallenged with noninvasive S. pneumoniae serotype 14 (Spn14) or S. pneumoniae serotype 19A (Spn19A). The coinfections were followed by comparative analyses of inflammatory responses and animal protection. We found that resident alveolar macrophages are efficient in the clearance of both pneumococcal serotypes in the absence of influenza infection; in contrast, they are essential for airway control of Spn14 infection but not Spn19A infection. In agreement, TNF-a and neutrophils play a compensatory protective role in secondary bacterial infection associated with Spn19A; however, the essential requirement for alveolar macrophage–mediated clearance significantly enhances the virulence of Spn14 during postinfluenza pneumococcal infection. Furthermore, we show that, although IL-1 signaling is not required for host defense against pneumococcal infection alone, it is essential for sustaining antibacterial immunity during postinfluenza pneumococcal infection, as evidenced by significantly aggravated bacterial burden and animal mortality in Il1r1 2 / 2 mice. Mechanistically, we show that through preventing alveolar macrophage depletion, inflammatory cytokine IL-1 signaling is critically involved in host resistance to influenza and pneumococcal coinfection. The Journal of Immunology, 2018, 200: 1425–1433.

Original languageEnglish (US)
Pages (from-to)1425-1433
Number of pages9
JournalJournal of Immunology
Volume200
Issue number4
DOIs
StatePublished - Feb 15 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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