Plasmodium remains a major pathogen causing
malaria and impairing defense against other
infections. Defining how Plasmodium increases susceptibility to heterologous pathogens may lead to interventions that mitigate the severity of
coinfections. Previous studies proposed that reduced T cell responses during
coinfections are due to diminished recruitment of naive T cells through
infection-induced decreases in
chemokine CCL21. We found that, although
Listeria infections reduced expression of CCL21 in murine spleens, lymphocytic choriomeningitis virus (LCMV)-specific T cell responses were not impaired during Listeria + LCMV
coinfection, arguing against a major role for this
chemokine in
coinfection-induced T cell suppression. In our experiments, Plasmodium yoelii
infection led to a reduced CD8(+) T cell response to a subsequent
Listeria infection. We propose an alternative mechanism whereby P. yoelii suppresses Listeria-specific T cell responses. We found that Listeria-specific T cells expanded more slowly and resulted in lower numbers in response to
coinfection with P. yoelii. Mathematical modeling and experimentation revealed greater apoptosis of Listeria-specific effector T cells as the main mechanism, because P. yoelii
infections did not suppress the recruitment or proliferation rates of Listeria-specific T cells. Our results suggest that P. yoelii
infections suppress immunity to Listeria by causing increased apoptosis in Listeria-specific T cells, resulting in a slower expansion rate of T cell responses.