Susceptibility to infectious diseases: Leishmania as a paradigm

The diverse response of individuals within populations to infectious pathog ens remains poorly understood, although genetic determinants undoubtedly co ntribute in substantial ways to the outcome of infection. In a mouse model of infection with the intramacrophage protozoan Leishmania major, susceptib ility correlates both with aberrant helper T cell differentiation biased to wards the production of interleukin 4 and with the presence of an endogenou s CD4 T cell repertoire that recognizes an immunodominant parasite antigen with high frequency. In the setting of the particular ecological niche occu pied by Leishmania, this combination of otherwise unrelated factors synergi zes to result in exquisite susceptibility to this single pathogen, without seemingly compromising host defenses against other agents. Similar paradigm s could underlie susceptibility to other pathogenic organisms.