Corynebacterium pseudodiphtheriticum is a Gram-positive bacterium found as a member of the normal microbiota of the upper respiratory tract. It was suggested that C. pseudodiphtheriticum may be potentially used as a next-generation probiotic for nasal application, although no deep studies were performed in this regard. We hypothesized that human isolate C. pseudodiphtheriticum strain 090104 is able to modulate the respiratory innate immune response and beneficially influence the resistance to viral and bacterial infections. Therefore, in the present study we investigated how the exposure of infant mice to nasal priming with viable or non-viable C. pseudodiphtheriticum 090104 influences the respiratory innate immune response triggered by Toll-like receptor (TLR)-3 activation, the susceptibility to primary Respiratory Synsytial Virus (RSV) infection, and the resistance to secondary Streptococcus pneumoniae pneumonia. We demonstrated that the nasal priming with viable C. pseudodiphtheriticum 090104 differentially modulated TLR3-mediated innate antiviral immune response in the respiratory tract of infant mice, improving their resistance to primary RSV infection, and secondary pneumococcal pneumonia. In association with the protection against RSV-pneumococcal superinfection, we found that viable C. pseudodiphtheriticum improved lung CD3+CD4+IFN-γ+, and CD3+CD4+IL-10+ T cells as well as CD11c+SiglecF+IFN-β+ alveolar macrophages. Of interest, non-viable bacteria did not have the same protective effect, suggesting that C. pseudodiphtheriticum colonization is needed for achieving its protective effect. In conclusion, we present evidence that nasal application of viable C. pseudodiphtheriticum could be thought as an alternative to boost defenses against RSV and secondary pneumococcal pneumonia, which should be further studied and validated in clinical trials. Due to the absence of a long-lasting immunity, re-infection with RSV throughout life is common. Thus, a possible perspective use could be a seasonal application of a nasal probiotic spray to boost respiratory innate immunity in immunocompetent subjects.

While it is now acknowledged that CD4+ T cells expressing CD25 and Foxp3 (Treg cells) regulate immune responses and, consequently, influence the pathogenesis of infectious diseases, the regulatory response mediated by Treg cells upon infection by Trypanosoma cruzi was still poorly characterized. In order to understand the role of Treg cells during infection by this protozoan parasite, we determined in time and space the magnitude of the regulatory response and the phenotypic, functional and transcriptional features of the Treg cell population in infected mice. Contrary to the accumulation of Treg cells reported in most chronic infections in mice and humans, experimental T. cruzi infection was characterized by sustained numbers but decreased relative frequency of Treg cells. The reduction in Treg cell frequency resulted from a massive accumulation of effector immune cells, and inversely correlated with the magnitude of the effector immune response as well as with emergence of acute immunopathology. In order to understand the causes underlying the marked reduction in Treg cell frequency, we evaluated the dynamics of the Treg cell population and found a low proliferation rate and limited accrual of peripheral Treg cells during infection. We also observed that Treg cells became activated and acquired a phenotypic and transcriptional profile consistent with suppression of type 1 inflammatory responses. To assess the biological relevance of the relative reduction in Treg cells frequency observed during T. cruzi infection, we transferred in vitro differentiated Treg cells at early moments, when the deregulation of the ratio between regulatory and conventional T cells becomes significant. Intravenous injection of Treg cells dampened parasite-specific CD8+ T cell immunity and affected parasite control in blood and tissues. Altogether, our results show that limited Treg cell response during the acute phase of T. cruzi infection enables the emergence of protective anti-parasite CD8+ T cell immunity and critically influences host resistance.

Acetyl-salicylic acid (ASA) is a nonsteroidal antiinflammatory/analgesic drug, which may cause gastritis or stomach ulcers if intensively employed. Exopolysaccharide (EPS)-producing lactic acid bacteria have been claimed to induce immunostimulatory/antiulcer effects in the host. This study investigated the potential preventive effect of fermented milks (FM) with EPS-producing Streptococcus thermophilus strains (CRL 1190 and CRL 804) on an in vivo model of chronic gastritis. Fermented milks (2 EPS(+) and 1 EPS(-), separately) were fed to BALB/c mice for 7 d before inducing gastritis with ASA (400 mg/kg of body weight per day for 10 d; gastritis group, n = 5). Appropriate control groups (ASA administered but not given FM, n = 5; and ASA not administered but given FM) were included in this study. Gastric inflammatory activity was evaluated through the stomach's histology and the number of IFNgamma(+) and IL-10(+) cytokine-producing cells in the gastric mucosa. Only mice preventively treated with the EPS-producing Strep. thermophilus CRL 1190 FM and later administered ASA did not develop gastritis, showing a conserved gastric mucosa structure similar to those of healthy mice. A marked decrease of IFNgamma(+)- and increase of IL-10(+)-producing cells compared with the gastritis group mice were observed. Purified EPS from Strep. thermophilus CRL 1190 resuspended in autoclaved milk was also effective for gastritis prevention. The EPS-protein interaction might be responsible for the observed gastroprotective effect; such interactions may be affected by industrial manufacturing conditions. The results indicate that the FM with Strep. thermophilus CRL 1190 or its EPS could be used in novel functional foods for preventing chronic gastritis.