ABSTRACT
Animals have evolved two defense strategies to survive infections. Antagonistic strategies include mechanisms of immune resistance that operate to sense and 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. Host immune protection was dependent on systemic antibody responses and pathogen virulence behavior, rather than the recognition of specific virulent factor antigens. Finally, we demonstrate that an avirulent strain of C. rodentium commonly used in the field has background mutations in two genes that are important for LPS structure, which may complicate interpretations of previous studies in the field. Our work reveals novel insight into how asymptomatic infections can arise mechanistically with immune resistance, mediating exclusion of phenotypically virulent enteric pathogen to promote asymptomatic carriage.
Competing Interest Statement
The authors have declared no competing interest.
