Effect of Jun N-terminal kinase 1 and 2 on the replication of Penicillium marneffei in human macrophages

• Activation of JNK1/2 in macrophages infected with Penicillium marneffei.
• Role of JNK1/2 in TNF-α and IL-10 secretion in P. marneffei-infected macrophages.
• Effect of JNK1/2 on phagosomal maturation in P. marneffei-infected macrophages.
• Effect of JNK1/2 on intracellular multiplication of P. marneffei in macrophages.

Penicillium marneffei (P. marneffei) is a human pathogen which persists in macrophages and threatens the immunocompromised patients. To clarify the mechanisms involved, we evaluated the effect of c-Jun N-terminal kinase 1 and 2 (JNK1/2) on cytokine expression, phagosomal maturation and multiplication of P. marneffei in P. marneffei-stimulated human macrophages. P. marneffei induced the rapid phosphorylation of JNK1/2. Using the specific inhibitor of JNK1/2 (SP600125), we found that the inhibition of JNK1/2 suppressed P. marneffei-induced tumor necrosis factor-α and IL-10 production. In addition, the presence of SP600125 increased phagosomal acidification and maturation and decreased intracellular replication. These data suggest that JNK1/2 may play an important role in promoting the replication of P. marneffei. Our findings further indicate that the pathogen through the JNK1/2 pathway may attenuate the immune response and macrophage antifungal function.