The immunomodulatory capacity of a postbiotic depends on mucosal administration route

GUTIÉRREZ, FLORENCIA; VASILE, BRENDA; IVIR, MAXIMILIANO; ALVAREZ, SUSANA; SALVA, SUSANA

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2022

Sociedad Argentina de Inmunología

The nasal administration of Lacticaseibacillus rhamnosus CRL1505 peptidoglycan (PG), not their cell wall (CW), increases the infection resistance against Streptococcus pneumoniae (Sp), and improves innate and adaptive immune response in immunocompromised mice. In addition, the immunomodulatory effects of PG are a strain specific property. However, the oral administration of CW is more effective than the PG to improve bone marrow (BM) myelopiesis in immunocompromised mice. In this work, we compared the immunomodulatory capacity of PG and CW, before and after simulation of gastrointestinal digestion by in vitro and in vivo studies. First, in vitro colony-forming unit assays were performed to assess whether the clonogenic capacity of BM cells responded to direct interaction with L. rhamnosus (Lr) and its postbiotics. For this, mouse BM cells were plated in the presence or absence of Lr, PG or CW in culture medium for the granulocyte/macrophage forming unit (CFU-GM) (MethoCult™). Besides, the effect of splenocytes, HTL929 and RAW cells supernatants conditioned with Lr or its postbiotics was investigated. The counts and the phenotypic characterization of the colonies obtained were determined. We found that only Lr was able to increase clonogenic activity by directly stimulating BM cells. Surprisingly, in indirect assays, PG-conditioned HTL929 supernatants were the only ones to show increased clonogenic activity. Then, CW was incubated in a solution of simulated gastric and intestinal juice. Finally, 6-week-old Swiss albino mice received 2d nasal instillation of 8 µg/mice of PG (positive control), untreated CW (negative control), or treated CW. On d3, mice were challenged with Sp (107 CFU/ml). At 2d post-infection, we found that the treated CW was able to prevent the passage of Sp into the blood and reduce the lung counts as well as PG. Thus, the gastrointestinal passage of CW is necessary for the bioactive component of L. rhamnosus CRL1505 to exert its beneficial effect.