The study investigates the role of commensal bacteria in regulating immune responses to respiratory influenza virus infection. The researchers found that antibiotic treatment, particularly with neomycin, significantly impaired the generation of virus-specific CD4 and CD8 T cells and antibody responses. This impairment was not due to general immune deficiencies but was specifically linked to the activation of inflammasomes, which are crucial for cytokine production. The presence of neomycin-sensitive bacteria was associated with improved immune responses, suggesting their importance in maintaining a robust immune environment. The study also showed that local or distal injection of Toll-like receptor (TLR) ligands could rescue the immune impairment in antibiotic-treated mice, indicating that signals from commensal bacteria are essential for proper immune activation. These findings highlight the critical role of commensal microbiota in regulating respiratory mucosal immunity through the activation of inflammasomes.The study investigates the role of commensal bacteria in regulating immune responses to respiratory influenza virus infection. The researchers found that antibiotic treatment, particularly with neomycin, significantly impaired the generation of virus-specific CD4 and CD8 T cells and antibody responses. This impairment was not due to general immune deficiencies but was specifically linked to the activation of inflammasomes, which are crucial for cytokine production. The presence of neomycin-sensitive bacteria was associated with improved immune responses, suggesting their importance in maintaining a robust immune environment. The study also showed that local or distal injection of Toll-like receptor (TLR) ligands could rescue the immune impairment in antibiotic-treated mice, indicating that signals from commensal bacteria are essential for proper immune activation. These findings highlight the critical role of commensal microbiota in regulating respiratory mucosal immunity through the activation of inflammasomes.