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

Author:
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
Source:
Parasitology research 2019 v.118 no.1 pp. 63-71
ISSN:
0932-0113
Subject:
Leishmania donovani, blood serum, cell lines, enzymes, immune response, kinetoplast DNA, macrophages, malnutrition, mice, models, nutrition, parasite load, parasites, patients, retinoic acid, visceral leishmaniasis
Abstract:
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
Agid:
6272763