Annu Rev Microbiol 68:217C235. the dysbiosis caused by antibiotic treatment affects CD4+ T cell generation and PD-1 expression on CD4+ T cells and thereby perturbs plasma cell differentiation. Our results have revealed the importance of commensal microbes in modulating host immune responses to infection and support the possibility of controlling the severity of infection in humans by manipulating the microbiota. KEYWORDS: strains keep circulating in many countries with high vaccine coverage, and reports of an increasing incidence of infection worldwide have been accumulating for the past 20?years (3,C5). The reemergence of pertussis cases has partially been attributed to the waning immunity conferred by current acellular pertussis vaccines, medical advancements that have allowed more effective diagnosis and reporting of pertussis cases, the asymptomatic transmission of from individuals vaccinated with the acellular pertussis vaccine, evolving variant strains of circulating strains against which humans are less protected by the vaccine, and a decrease in vaccine coverage, which has compromised herd/community immunity (6, 7). Several virulence factors, such as pertussis toxin (PT), adenylate cyclase Gemcabene calcium toxin (AC), dermonecrotic toxin (DNT), and tracheal cytotoxin (TCT), have been shown to play pivotal roles in pathogenesis (1, 2, 8). Protection against infection is mediated by the innate and adaptive immune responses, and complete bacterial clearance requires both cell-mediated and humoral responses (9). However, combined data from clinical and animal studies showed that infection. Antibodies against major virulence factors are capable of preventing bacterial colonization by blocking adherence Mmp10 of the bacteria to human epithelial cells (10). The importance of B cells and antibodies in the protection against infection has also been demonstrated in studies using Ig?/? knockout mice (11). In addition, passive transfer experiments in animals showed that passively transferred anti-antibodies protected naive mice and piglets against challenge (12, 13). Long-term infection by is mainly caused by the ability of to interfere with the hosts innate and adaptive immune systems. Despite great advances in our understanding of virulence factors, the interplay between the pathogen and the host, especially the host microecology, still remains poorly understood. Commensal microbes can influence multiple aspects of host physiology (14), including host susceptibility to numerous diseases (15,C19). Indeed, the intestinal microbiota has emerged as a positive player Gemcabene calcium in the host defense system, supporting mucosal immunity and potentially modulating systemic immunity (20,C23). The effect of the gut microbiota on the immune responses in distal mucosal sites and its impact on the outcome of respiratory infections have recently been posed. In this regard, some Gemcabene calcium studies have shown that the gut microbiota plays a crucial role in the response to bacterial and viral respiratory infections (24,C28). Recently, several studies have shown that dysbiosis of the microbiota can cause long-lived immunological scarring, Gemcabene calcium Gemcabene calcium with profound effects on host immunity (29,C31). Ruiz et al. showed that a single early-life macrolide course can alter the microbiota and modulate host immune phenotypes and that these effects persist long after the antibiotic exposure has ceased (29). In addition, they showed that early-life antibiotic exposure has lasting and transferable effects on the microbial community network topology (29). One aspect of infection that remains largely unexplored is the role of the host microbiota in pathogenesis. To date, only one study has focused on the role of the nasal resident microbiota in bacterial competition with initial colonization and host selection during infection (32), where the authors showed that the removal of resident microorganisms from the nasal cavity allowed to efficiently colonize the murine nasal cavity and that the reintroduction of a single nasal cavity bacterial species was sufficient to block colonization in mice. However, the exact mechanisms by which commensal microbes prevent colonization are still unclear. In the present study, we investigated the impact of commensal microbes on host immune responses during infection. We found that.