Cooperation between physiological defenses and immune resistance produces asymptomatic carriage of a lethal bacterial pathogen

Animals evolved two defense strategies to survive infections. Antagonistic strategies include immune resistance mechanisms that operate to kill invading pathogens. Cooperative or physiological defenses mediate host adaptation to the infected state, limiting physiological damage and disease, without killing the pathogen, and have been shown to cause asymptomatic carriage and transmission of lethal pathogens. Here, we demonstrate that physiological defenses cooperate with the adaptive immune response to generate long-term asymptomatic carriage of the lethal enteric murine pathogen, Citrobacter rodentium. Asymptomatic carriage of genetically virulent C. rodentium provided immune resistance against subsequent infections. Immune protection was dependent on systemic antibody responses and pathogen virulence behavior rather than the recognition of specific virulent antigens. Last, we demonstrate that an avirulent strain of C. rodentium in the field has background mutations in genes that are important for LPS structure. Our work reveals insight into how asymptomatic infections can arise mechanistically with immune resistance, mediating exclusion of phenotypically virulent enteric pathogen to promote asymptomatic carriage.

Automated summary

Animals have evolved two defense strategies against infections, antagonistic strategies that kill invading pathogens, and cooperative or physiological defenses that limit disease without killing the pathogen. This study shows how physiological defenses cooperate with the adaptive immune response to generate long-term asymptomatic carriage of a lethal pathogen, Citrobacter rodentium. Asymptomatic carriage of a virulent strain of C. rodentium provides immune resistance against subsequent infections, which is dependent on systemic antibody responses and pathogen virulence behavior. The study also reveals that an avirulent strain of C. rodentium in the wild has mutations in genes important for LPS structure.