Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study

Sci Rep. 2016 Dec 6;6:38532. doi: 10.1038/srep38532.

Abstract

Mixed viral and bacterial infections are widely described in community-acquired pneumonia; however, the clinical implications of co-infection on the associated immunopathology remain poorly studied. In this study, microRNA, mRNA and cytokine/chemokine secretion profiling were investigated for human monocyte-derived macrophages infected in-vitro with Influenza virus A/H1N1 and/or Streptococcus pneumoniae. We observed that the in-vitro co-infection synergistically increased interferon-γ-induced protein-10 (CXCL10, IP-10) expression compared to the singly-infected cells conditions. We demonstrated that endogenous miRNA-200a-3p, whose expression was synergistically induced following co-infection, indirectly regulates CXCL10 expression by targeting suppressor of cytokine signaling-6 (SOCS-6), a well-known regulator of the JAK-STAT signaling pathway. Additionally, in a subsequent clinical pilot study, immunomodulators levels were evaluated in samples from 74 children (≤5 years-old) hospitalized with viral and/or bacterial community-acquired pneumonia. Clinically, among the 74 cases of pneumonia, patients with identified mixed-detection had significantly higher (3.6-fold) serum IP-10 levels than those with a single detection (P = 0.03), and were significantly associated with severe pneumonia (P < 0.01). This study demonstrates that viral and bacterial co-infection modulates the JAK-STAT signaling pathway and leads to exacerbated IP-10 expression, which could play a major role in the pathogenesis of pneumonia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bacterial Infections / immunology*
  • Bacterial Infections / microbiology
  • Bacterial Infections / virology
  • Base Sequence
  • Chemokine CXCL10 / metabolism*
  • Coinfection / immunology
  • Coinfection / microbiology*
  • Coinfection / virology*
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunity, Innate* / genetics
  • Infant
  • Influenza A Virus, H1N1 Subtype
  • Macrophages / immunology
  • Macrophages / microbiology
  • Macrophages / virology
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • Models, Biological
  • Pneumonia / immunology*
  • Pneumonia / microbiology*
  • Pneumonia / virology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Streptococcus pneumoniae
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Translational Medical Research
  • Virus Diseases / immunology*
  • Young Adult

Substances

  • CXCL10 protein, human
  • Chemokine CXCL10
  • MicroRNAs
  • RNA, Messenger
  • SOCS6 protein, human
  • Suppressor of Cytokine Signaling Proteins