A diverse community of trillions of commensal bacteria inhabits mucosal and epidermal surfaces in humans and plays an important role in defense against pathogens, including respiratory pathogens. Commensal bacteria act on the host's immune system to induce protective responses that prevent colonization and invasion by pathogens. On the other hand, these bacteria can directly inhibit the growth of respiratory pathogens by producing antimicrobial products/signals and competing for nutrients and adhesion sites. Such mechanisms preserve the niche for commensal bacteria and support the host in containing respiratory infections. Herein, we discuss current evidence on the role of commensal bacteria in conferring protection against respiratory pathogens and the underlying mechanisms by which these bacteria do so. A deeper knowledge of how commensal bacteria interact with the host and pathogens might provide new insights that are poised to aid in the development of vaccines and therapeutics that target infectious diseases.

Although antibiotics confer significant health benefits in treating or preventing bacterial infections, an accumulating wealth of evidence illustrates their detrimental effect on host-microbiota homeostasis, posing a serious menace to the global public health. In recent years, it is becoming evident that infants, who are subjected to frequent antibiotic exposures due to their vulnerability to infection, reflect increased susceptibility to a wide spectrum of diseases, including infection, in later life. Antibiotics induce perturbations of the microbiota or dysbiosis, which in turn alters the host immune responses against pathogens. In comparison with adults, antibiotic treatments in infants have disproportionate consequences because the infant microbiota represents an evolving system that is unstable and immature until 2–3 years of age. However, relatively less knowledge is available on how antibiotics affect the infant microbiota and immunity. In this review article, we focus on how antibiotic treatment regimens influence the infant innate and adaptive immunity to pathogens in humans and animal models, and make the host susceptible to infections in later life. There is a critical need to better understand the effect of antibiotics on infant immune function, which may have implications for developing effective prophylactics and therapeutics against diseases in infants and adults.

Streptococcus pneumoniae causes various diseases worldwide. Current pneumococcal vaccines protect against a limited number of more than 90 pneumococcal serotypes, accentuating the urgent need to develop novel prophylactic strategies. S. pneumoniae and the commensal Streptococcus mitis share immunogenic characteristics that make S. mitis an attractive vaccine candidate against S. pneumoniae . In this study, we evaluated the potential of S. mitis and its mutant expressing pneumococcal capsule type 4 ( S. mitis TIGR4cps) to induce protection against S. pneumoniae lung infection in mice. Our findings show that intranasal vaccination with S. mitis protects against S. pneumoniae strains D39 (serotype 2) and TIGR4 (serotype 4) in a serotype-independent fashion, which is associated with enhanced antibody and T cell responses. Furthermore, S. mitis TIGR4cps conferred additional protection against S. pneumoniae TIGR4, but not against D39. The findings highlight the potential of S. mitis to generate protection that combines both serotype-independent and serotype-specific responses.

Two recent studies have highlighted the potential of nasal microbiota transplantation (NMT) to treat chronic rhinosinusitis (CRS). Here we evaluate these findings and propose that lessons from fecal microbiota transplantation (FMT) could guide NMT development, with possible implications for combating antimicrobial resistance in respiratory infections.

Recent studies have identified semaphorin 3E (Sema3E) as a novel mediator of immune responses. However, its function in immunity to infection has yet to be investigated. Using a mouse model of chlamydial lung infection, we show that Sema3E plays a significant role in the host immune response to the infection. We found that Sema3E is induced in the lung after chlamydial infection, and Sema3E deficiency has a detrimental impact on disease course, dendritic cell (DC) function, and T cell responses. Specifically, we found that Sema3E knockout (KO) mice exhibited higher bacterial burden, severe body weight loss, and pathological changes after Chlamydia muridarum lung infection compared with wild-type (WT) mice. The severity of disease in Sema3E KO mice was correlated with reduced Th1/Th17 cytokine responses, increased Th2 response, altered Ab response, and a higher number of regulatory CD4 T cells. Moreover, DCs isolated from Sema3E KO mice showed lower surface expression of costimulatory molecules and production of IL-12, but higher expression of PD-L1, PD-L2, and IL-10 production. Functional DC–T cell coculture studies revealed that DCs from infected Sema3E KO mice failed to induce Th1 and Th17 cell responses compared with DCs from infected WT mice. Upon adoptive transfer, mice receiving DCs from Sema3E KO mice, unlike those receiving DCs from WT mice, were not protected against challenge infection. In conclusion, our data evidenced that Sema3E acts as a critical factor for protective immunity against intracellular bacterial infection by modulating DC functions and T cell subsets. Key Points Semaphorin 3E protects against chlamydial lung infection. Semaphorin 3E modulates DC and T cell function for effective immune response.