Peptidoglycan from Lactobacillus rhamnosus CRL1505 beneficially modulate the respiratory inflammatory response triggered by Toll-like receptor 3 activation

SALVA, SUSANA; CHIBA, ERIKA; ZELAYA, HORTENSIA; KOLLING, YANINA; KITAZAWA, HARUKI; ALVAREZ, SUSANA; VILLENA, JULIO

San Miguel de Tucumán

Simposio; IV International Symposium on Lactic Acid Bacteria - Food, Health and Applications; 2013

Centro de Referencia para Lactobacilos. CERELA-CONICET

We have previously demonstrated that nasally administered Lactobacillus rhamnosus CRL1505 (Lr1505) beneficially modulate the inflammatory response triggered by the activation of Toll-like receptor (TLR)-3 and the outcome of Respiratory Syncytial Virus (RSV) infection. In this work, we aimed to advance in the knowledge of the mechanism(s) involved in the immunoregulatory effect of Lr1505 by evaluating the capacity of its peptidoglycan (Pg1505) to regulate the respiratory antiviral response. To mimic the pro-inflammatory and physiopathological consequences of RNA viral infections in the lung, we used an experimental model of lung inflammation based on the administration of the artificial viral pathogen-associated molecular pattern poly(I:C). Six-week old BALB/c mice were treated with Pg1505 (equivalent to 108 cells of Lr1505) by the nasal route during two consecutive days. Pg1505-treated and untreated control mice were then nasally challenged with 250 ìg poly(I:C) (equivalent to 10 mg/kg body weight). Mice received three doses of poly(I:C) with 24 hours rest period between each administration. Lung tissue damage and respiratory and systemic immune responses were studied at several time points after the last administration of poly(I:C). Nasal challenge with poly(I:C) induced a marked impairment of lung function that was accompanied by the production of pro-inflammatory mediators and inflammatory cell recruitment into the airways as we previously described. The preventive administration of Pg1505 reduced lung injuries and the production of TNF-á, IL-6, IL-8 and MCP-1 in the respiratory tract after the challenge with poly(I:C) (p<0.05). Moreover, Pg1505 induced a significant increase in lung and serum IL-10 (p<0.01). We also observed that Pg1505 was able to increase respiratory IFN-ã levels and the number of lung CD3+CD4+IFN-ã+ T cells after poly(I:C) challenge. In addition, higher numbers of both CD103+ and CD11bhigh dendritic cells and increased expression of MHC-II, IL-12 and IFN-ã in these cell populations were found in lungs of Pg1505-treated mice (p<0.05). Therefore, we demonstrated in this work that Pg1505 treatment beneficially regulate the balance between pro-inflammatory mediators and IL-10 after respiratory TLR3 activation, allowing an effective inflammatory response and avoiding tissue damage. These protective effects were similar to those previously observed for Lr1505. Therefore, Lr1505 in the form of live cells may not be required for enhancing respiratory defences against viral pathogens. Our present results show that cellular fractions of probiotic bacteria such as Pg1505 could be an interesting alternative as mucosal adjuvants, especially in immunocompromised hosts in which the use of live bacteria might be dangerous. In addition, cellular fractions have the advantages of allowing a longer product shelf-life, easier storage, and transportation.