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Leishmania donovani reduces the levels of retinoic acid–synthesizing enzymes in infected macrophages and favoring its own survival

Verma, Pankaj, Kureel, Amit Kumar, Saini, Sheetal, Prakash, Satya, Kumari, Smita, Kottarath, Sarath Kumar, Srivastava, Sandeep Kumar, Bhat, Madhusudan, Dinda, Amit Kumar, Thakur, Chandreshwar Prasad, Sharma, Shivesh, Rai, Ambak Kumar
Parasitology research 2019 v.118 no.1 pp. 63-71
Leishmania donovani, blood serum, cell lines, enzymes, immune response, kinetoplast DNA, macrophages, malnutrition, mice, models, nutrition, parasite load, parasites, patients, retinoic acid, visceral leishmaniasis
People suffering from malnutrition become susceptible to the infection like Leishmania sp., as it results in a compromised immune response. Retinoic acid (RA), an important constituent of nutrition, shows an immune-modulatory activity. However, its role in the containment of infection is not yet ascertained, particularly in case of visceral leishmaniasis (VL). VL patients (n = 10) and healthy endemic controls (n = 9) were recruited to measure the serum levels of RA. An in vitro model of Leishmania infection using the murine mφ cell line J774.1 was used to investigate the RA-synthesizing enzymes (RALDH-1 and RALDH-2). Parasite loads among infected mφ were measured by quantitative expression of kDNA in the presence of an inhibitor of the RALDH-2 enzyme. We found a significant decrease in the serum levels of RA in VL cases. Importantly, we observed decreased levels of RALDH-1 and RALDH-2 among L. donovani–infected mφ along with simultaneous decrease as well as increase in the Th-1 and Th-2-associated factors, respectively. Furthermore, the pretreatment of mφ with an RALDH-2 inhibitor improved parasite in vitro infection. Our findings show impaired RA pathway among infected mφ and indicate that an intact RA pathway is critical for anti-Leishmania immune response. Graphical abstract ᅟ