Testosterone attenuates p38 MAPK pathway during Leishmania donovani infection of macrophages.

Leishmania donovani (L. donovani) is an obligatory intracellular pathogen that resides and multiplies in the macrophages and has been found to alter the signaling parameters of the host. Testosterone plays a key role as signaling molecules in the regulation of parasite infections and could increase L. donovani infection of macrophages. The mitogen-activated protein kinases (MAPKs) pathway participates in the regulation of functions involved in parasite infection and host defense. In this work, the possibility that modulation of components of MAPK signaling may participate in the L. donovani infection was investigated. We found in this study that L. donovani infection upregulated p38 MAPK of bone marrow-derived macrophage, but not the other MAPK families, extracellular signal-related kinase 1 and 2, and c-jun N-terminal kinase (JNK), as evaluated by Western blotting with specific anti-MAPK antibodies. Moreover, we found that testosterone did not in itself interfere with the MAPKs but attenuated the L. donovani activation of p38 MAPK. The inhibition of p38 MAPK might be responsible for the testosterone-induced higher L. donovani infection since SB203580, a specific inhibitor of p38 MAPK, augmented L. donovani infection too. Collectively, our data indicated that the testosterone-enhanced L. donovani survival in macrophages might be due to the attenuation of MAPK signaling pathway by testosterone.