Humoral immunity in leishmaniasis – Prevention or promotion of parasite growth?

Leishmaniasis can present as a “spectrum” of clinical outcomes. There is evidence that these divergent clinical outcomes are attributable to genetic differences in the human host [1] as well the species of infecting parasite [2]. The spectrum of disease has largely been described by defining the polar opposites of T cell immune responses. In the mouse model, a T(H)1 immune response is associated with low numbers of Leishmania parasites in lesions, whereas a T(H)2 immune response has been associated with unrestricted parasite growth. In the present work, we revisit leishmaniasis and seek to better define the clinical spectrum as a function of divergent humoral immune responses. We describe examples in human, canine, and even some murine models of leishmaniasis that reveal a direct correlation between high anti-parasite antibody responses and unrestricted parasite growth. Therefore, we propose that the spectral nature of this disease may be due to quantitative and qualitative differences in the antibodies that are produced during disease. In human visceral leishmaniasis, a decrease in anti-parasite antibody levels may actually predict disease resolution. Thus, rather than defining this disease as a simple T(H)1/T(H)2 dichotomy, we propose that clinical leishmaniasis depends on the degree of humoral immunity, with high IgG predicting parasite persistence. These observations have obvious implications for vaccine development in leishmaniasis, and they may extend to other diseases caused by intracellular pathogens.