Visceral leishmaniasis is a neglected tropical disease caused by
Leishmania (L.) donovani
parasite in the Indian subcontinent. Macrophages (mϕ) are the harboring cells for parasite and their interactions dictate the pathogenesis of this disease. Polyunsaturated fatty acids are an integral part of the mϕ cell membrane and are derived from linoleic acid (LA), which is a principal essential fatty acid. Here, we have investigated the effect of the simultaneous presence of LA during
L. donovani
infection in mϕ. Treatment with LA suppresses the parasitic load in mϕ (kDNA expression) and promotes the Th-1 type immune response (IL-12, iNOS). However, no significant change in kDNA expressions was observed when
L. donovani
promastigotes were treated with LA. Intrigued by this observation, we explored mechanism(s) by which LA promoted the protective type immune response in infected mϕ. Interestingly, LA decreased the release of
L. donovani
derived extracellular vesicle later characterized as microvesicles. Moreover, these microvesicles were suppressive concerning their bias toward the Th-2 type of immune responses (IL-10, Arginase) in mϕ. We suggest that LA plays a protective role in the immune response against
L. donovani
infection by inhibiting the release to
Leishmania
derived microvesicles and thus promoting Th-1 type immune response in mϕ.