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

HORTENSIA ZELAYA; ASUKA TADA; GUADALUPE VIZOSO PINTO; SUSANA SALVA; PAULRAJ KANMANI; GRACIELA AGÜERO; SUSANA ALVAREZ; HARUKI KITAZAWA; JULIO VILLENA

INFLAMMATION RESEARCH

BIRKHAUSER VERLAG AG

Lugar: BASEL; Año: 2015 vol. 64 p. 589 - 602

1023-3830

The aim of this work was to evaluate whether the nasal administration of live and heat-killed immunobiotic strain Lactobacillus rhamnosus CRL1505 were able to beneficially modulate the immune-coagulative response during influenza virus (IFV) infection in order to improve survival and reduce lung injury. We found that both viable and non-viable L. rhamnosus CRL1505 were able to protect mice challenged with IFV. We unraveled three mechanisms by which this immunobiotic strain protected infected mice by reducing pulmonary injury and lung viral loads: a) Inflammatory response was improved early after IFV infection, and efficiently regulated later, allowing higher clearance of virus together with a reduction of inflammatory lung tissue damage. This latter effect was associated to the higher levels of the regulatory cytokine IL-10. b) Innate and adaptive antiviral immune responses were enhanced as shown by the improved levels of type I interferons (IFNs), CD4+IFN-γ+ lymphocytes, and lung CD11c+CD11blowCD103+ and CD11c+CD11bhighCD103- dendritic cells. c) The pro-coagulation state induced by IFV infection was reversed mainly by down-regulating lung tissue factor expression and restoring thrombomodulin levels. In addition, our results demonstrated that the capacity of L. rhamnosus CRL1505 to improve the outcome of IFV infection would be related to its ability to beneficially modulate lung TLR3-triggered immune response. Although several other works have demonstrated the capacity of immunobiotic lactobacilli to improve defenses against influenza, our work is the first in demonstrate the ability of an immunobiotic strain to beneficially modulate inflammation-coagulation interactions during IFV infection.