Commensal bacteria regulate immune responses to respiratory influenza A virus infection. The study shows that the composition of the commensal microbiota critically influences the generation of virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection. Antibiotic treatment reduced immune responses, but local or distal injection of Toll-like receptor (TLR) ligands could restore immune function. Intact microbiota provided signals leading to the expression of pro-IL-1β and pro-IL-18 mRNA at steady state. Following influenza virus infection, inflammasome activation led to the migration of dendritic cells (DCs) from the lung to the draining lymph node and T-cell priming. The study reveals the importance of commensal microbiota in regulating immunity in the respiratory mucosa through the proper activation of inflammasomes. Commensal bacteria are essential in shaping intestinal immune responses. Germ-free mice have underdeveloped gut-associated lymphoid tissues. Commensal bacteria are sensed by the innate pattern-recognition receptors to maintain the homeostasis of intestinal epithelial cell turnover and integrity. Gut commensal microbiota also support intestinal immune homeostasis by regulating Tregs and Th17 cells. In some instances, specific bacteria have been associated with immunological outcomes. Commensal bacteria, particularly the segmented filamentous bacteria, promote Th17 development in the intestine. Recent studies highlight the importance of gut bacterial composition in a number of pathological conditions including diabetes and obesity. Inflammatory bowel disease can develop as a result of the emergence of harmful intestinal bacteria. However, it remains unclear whether there is a role for microbiota in shaping the immune inductive function at a nonintestinal mucosal surface such as the lung. The study examines the role of commensal bacteria in the initiation of adaptive immunity after respiratory infection with influenza virus. The study demonstrates the requirement for intact commensal bacterial community in the establishment of Th1, CTL, and IgA responses to respiratory influenza virus infection. Notably, the study found that neomycin-sensitive bacteria contributed to immunocompetence in the lung. This was in part mediated by providing signals for robust priming of pro-IL-1β and pro-IL-18 expression at steady state. Thus, the data reveal a key role for commensal bacteria in controlling adaptive immunity against a respiratory virus infection. Antibiotic treatment diminished immune responses to respiratory influenza virus infection. To determine the importance of commensal microbiota in immune responses within the respiratory tract, mice were subjected to a 4-week oral administration of antibiotic combination. This treatment resulted in significant changes in the composition of culturable commensal bacteria. Antibiotic-treated mice were then infected intranasally with a sublethal dose of A/PR8 influenza virus. Mice were kept on the V/N/M/A regimen for the entire duration of the experiments. Two weeks later, virion-specific Ig levelsCommensal bacteria regulate immune responses to respiratory influenza A virus infection. The study shows that the composition of the commensal microbiota critically influences the generation of virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection. Antibiotic treatment reduced immune responses, but local or distal injection of Toll-like receptor (TLR) ligands could restore immune function. Intact microbiota provided signals leading to the expression of pro-IL-1β and pro-IL-18 mRNA at steady state. Following influenza virus infection, inflammasome activation led to the migration of dendritic cells (DCs) from the lung to the draining lymph node and T-cell priming. The study reveals the importance of commensal microbiota in regulating immunity in the respiratory mucosa through the proper activation of inflammasomes. Commensal bacteria are essential in shaping intestinal immune responses. Germ-free mice have underdeveloped gut-associated lymphoid tissues. Commensal bacteria are sensed by the innate pattern-recognition receptors to maintain the homeostasis of intestinal epithelial cell turnover and integrity. Gut commensal microbiota also support intestinal immune homeostasis by regulating Tregs and Th17 cells. In some instances, specific bacteria have been associated with immunological outcomes. Commensal bacteria, particularly the segmented filamentous bacteria, promote Th17 development in the intestine. Recent studies highlight the importance of gut bacterial composition in a number of pathological conditions including diabetes and obesity. Inflammatory bowel disease can develop as a result of the emergence of harmful intestinal bacteria. However, it remains unclear whether there is a role for microbiota in shaping the immune inductive function at a nonintestinal mucosal surface such as the lung. The study examines the role of commensal bacteria in the initiation of adaptive immunity after respiratory infection with influenza virus. The study demonstrates the requirement for intact commensal bacterial community in the establishment of Th1, CTL, and IgA responses to respiratory influenza virus infection. Notably, the study found that neomycin-sensitive bacteria contributed to immunocompetence in the lung. This was in part mediated by providing signals for robust priming of pro-IL-1β and pro-IL-18 expression at steady state. Thus, the data reveal a key role for commensal bacteria in controlling adaptive immunity against a respiratory virus infection. Antibiotic treatment diminished immune responses to respiratory influenza virus infection. To determine the importance of commensal microbiota in immune responses within the respiratory tract, mice were subjected to a 4-week oral administration of antibiotic combination. This treatment resulted in significant changes in the composition of culturable commensal bacteria. Antibiotic-treated mice were then infected intranasally with a sublethal dose of A/PR8 influenza virus. Mice were kept on the V/N/M/A regimen for the entire duration of the experiments. Two weeks later, virion-specific Ig levels