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

Jonathan Hoffmann (1) , Daniela Machado (1) , Olivier Terrier (2) , Stephane Pouzol (1) , Mélina Messaoudi (1) , Wilma Basualdo (3) , Emilio E. Espinola (4) , Rosa M. Guillen (4) , Manuel Rosa-Calatrava (2) , Valentina Picot (1) , Thomas Bénet (5, 1) , Hubert Endtz (1) , Graciela Russomando (4) , Gláucia Paranhos-Baccalà (1)

1 LPE-Fondation Mérieux - Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory
2 Virpath - Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control
3 UNA - Universidad Nacional de Asunción [Paraguay] = National University of Asunción = Université nationale d'Asunción
4 Research Institut of Health
5 Service d'Hygiène, Epidémiologie et Prévention [Hôpital Edouard Herriot - HCL]

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 \textless 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.

Mots clés: Adult; Aged; Bacterial Infections; Base Sequence; Chemokine CXCL10; Coinfection; Female; Gene Expression Profiling; Humans; Immunity; Innate; Infant; Influenza A Virus; H1N1 Subtype; Macrophages; Male; MicroRNAs; Middle Aged; Models; Biological; Pneumonia; RNA; Messenger; Streptococcus pneumoniae; Suppressor of Cytokine Signaling Proteins; Translational Medical Research; Virus Diseases; Young Adult

Domaines: Immunologie; Bactériologie; Virologie

Jonathan Hoffmann, Daniela Machado, Olivier Terrier, Stephane Pouzol, Mélina Messaoudi, et al.. Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study. Scientific Reports, 2016, 6, pp.38532. ⟨10.1038/srep38532⟩. ⟨hal-01909045⟩