Nasal priming with immunobiotic Lactobacillus rhamnosus modulates inflammation–coagulation interactions and reduces influenza virus-associated pulmonary damage

Hortensia Zelaya, Asuka Tada, Maria Guadalupe Vizoso-Pinto, Susana Salva, Paulraj Kanmani, Graciela Agüero, Susana Alvarez, Haruki Kitazawa, Julio Villena

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Objective: To evaluate the effect of the nasal administration of live and heat-killed Lactobacillus rhamnosus CRL1505 (Lr1505) on immune-coagulative response during influenza virus (IFV) infection to improve survival and reduce lung injury. Methods: Six-week-old BALB/c mice were treated with live or heat-killed Lr1505 by the nasal route during two consecutive days. Treated and untreated control mice were then nasally challenged with IFV. Results: Both viable and non-viable Lr1505 protected infected mice by reducing pulmonary injury and lung viral loads trough several mechanisms: (a) Inflammatory cytokines were efficiently regulated allowing higher clearance of virus and reduction of inflammatory lung tissue damage, associated to higher levels of the regulatory cytokine IL-10. (b) The antiviral immune response was enhanced with improved levels of type I interferons, CD4+IFN-γ+ lymphocytes, and lung CD11c+CD11blowCD103+ and CD11c+CD11bhighCD103 dendritic cells. (c) The procoagulant state was reversed mainly by down-regulating tissue factor expression and restoring thrombomodulin levels in lung. The capacity of Lr1505 to improve the outcome of IFV infection would be related to its ability to beneficially modulate lung TLR3-triggered immune response. Conclusions: Our work is the first to demonstrate the ability of an immunobiotic strain to beneficially modulate inflammation–coagulation interactions during IFV infection. Interestingly, non-viable L. rhamnosus CRL1505 was as effective as the viable strain to beneficially modulate respiratory antiviral immune response.

Original languageEnglish
Pages (from-to)589-602
Number of pages14
JournalInflammation Research
Volume64
Issue number8
DOIs
Publication statusPublished - 2015 Aug 23

Keywords

  • Coagulation
  • Inflammation
  • Influenza virus
  • Lactobacillus rhamnosus CRL1505
  • Poly(I:C)
  • TLR3

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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