title: Nasal priming with immunobiotic Lactobacillus rhamnosus modulates inflammation-coagulation interactions and reduces influenza virus-associated pulmonary damage.
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(+)CD11b(low)CD103(+) and CD11c(+)CD11b(high)CD103(-) 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.
authors.affiliation: Immunobiotics Research Group, Tucumán, Argentina.
authors.forename: Hortensia
authors.initials: H
authors.lastname: Zelaya
authors.forename: Asuka
authors.initials: A
authors.lastname: Tada
authors.forename: Maria Guadalupe
authors.initials: MG
authors.lastname: Vizoso-Pinto
authors.forename: Susana
authors.initials: S
authors.lastname: Salva
authors.forename: Paulraj
authors.initials: P
authors.lastname: Kanmani
authors.forename: Graciela
authors.initials: G
authors.lastname: Agüero
authors.forename: Susana
authors.initials: S
authors.lastname: Alvarez
authors.forename: Haruki
authors.initials: H
authors.lastname: Kitazawa
authors.forename: Julio
authors.initials: J
authors.lastname: Villena
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology; D000281:Administration, Intranasal; D000818:Animals; D001777:Blood Coagulation; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology*; D052201:Lacticaseibacillus rhamnosus; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology; D010976:Platelet Count; D011070:Poly I-C / Q000494:pharmacology; D019936:Probiotics / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D011070:Poly I-C