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

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

Author information

1
Laboratoire des Pathogènes Émergents, Fondation Mérieux - CIRI - Inserm U1111, Lyon, France.
2
Virologie et Pathologie Humaine VirPath, CIRI - UCBL1 - Inserm U1111 - CNRS UMR 5308 - ENS de Lyon, Lyon, France.
3
Hospital General Pediátrico Niños de Acosta Ñu, Ministerio de Salud Pública y Bienestar Social, Paraguay.
4
Departamento de Biología Molecular y Biotecnologia, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Paraguay.
5
Infection Control and Epidemiology Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.

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.

PMID:
27922126
PMCID:
PMC5138590
DOI:
10.1038/srep38532
[Indexed for MEDLINE]
Free PMC Article

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