Lactobacillus rhamnosus CRL1505 peptidoglycan modulates the inflammation-coagulation response triggered by poly(I:C)

ZELAYA H; TADA A; CLÚA P; MARRANZINO G; SALVA S; ALVAREZ S; AGÜERO G; VILLENA J

Buenos Aires

Congreso; First LASID-SAI-FAIC Meeting, IV LASID Meeting, LXIII Argentinean Society for Immunology Meeting, II French-Argentinean Immunology Meeting; 2015

Sociedad Argentina de Inmunologìa

Presenting author´s: Hortensia Zelaya, hzelaya@fbqf.unt.edu.ar Lactobacillus rhamnosus CRL1505 PEPTIDOGLYCAN MODULATES THE INFLAMMATION-COAGULATION RESPONSE TRIGGERED BY POLY(I:C)Hortensia Zelaya1,2,5, Asuka Tada3,4, Patricia Clua1,2, Gabriela Marranzino1,2, Susana Salva1,2, Susana Alvarez1,2,5, Haruki Kitazawa3,4, Graciela Agüero1,5 and Julio Villena1,2,4 *1Immunobiotics Research Group, Argentina, 2CERELA-CONICET, Argentina, 3Food and Feed Immunology Group, Japan, 4Centre of Food and Agricultural Immunology-Tohoku University, Japan, 5UNT, Argentina.* Corresponding author. Mailing address for Julio Villena: Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET). Tucuman, Argentina. Phone: +54-381-4310465. Fax: +54-381-4005600. E-mail address: jcvillena@cerela.org.ar Background: Lactobacillus rhamnosus CRL1505 beneficially modulates inflammation-coagulation response during respiratory viral infections. This study evaluated the capacity of the peptidoglycan obtained from the CRL1505 strain (Pg1505) to modulate the immuno-coagulative response triggered by the viral pathogen associated molecular pattern poly(I:C).Methods: adult BALB/c mice were nasally treated with Pg1505 for 2 days. Treated and untreated control mice were then nasally challenged with poly(I:C). Mice received three doses of poly(I:C) with 24 hours rest period between each administration. The immune-coagulative response was studied after the last administration of poly(I:C).Results: poly(I:C) challenge significantly increased blood and respiratory proinflammatory mediators, decreased prothrombin activity (PT) and increased von Willebrand Factor (vWF) levels in plasma. Furthermore, tissue factor (TF) expression was elevated in lungs. These changes induced a significant damage in lung tissue. Pg1505-treated mice showed significantly increased levels of PT and lung TNF-α, reduced vWF and TF while the levels of IL-10 and thrombomodulin were higher than control mice. Those changes induced by Pg1505 correlated with a significant reduction of lung tissue damage. In vivo and complementary in vitro studies with RAW cells indicated that macrophages would be a key population for the protective effect of Pg1505, since reduced production of inflammatory mediators as well as TF were found in Pg1505-treated macrophages after poly(I:C) challenge. Conclusions: peptidoglycan from L. rhamnosus CRL1505 is able to beneficially modulate the immuno-coagulative response in the respiratory tract after TLR3 activation through its capacity to regulate respiratory macrophages production of inflammatory and procoagulant mediators. Keywords: hemostasis - inflammation - Lactobacillus rhamnosus CRL1505 peptidoglycan - poly (I:C) - macrophages