Leishmania donovani : Dynamics of L. donovani evasion of innate immune cell attack due to malnutrition in visceral leishmaniasis

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2014-04, Vol.30 (4), p.449-458
• Main Authors: Kumar, Vikash, M.Sc, Bimal, Sanjiva, Ph.D, Singh, Shubhankar K., Ph.D, Chaudhary, Rajesh, M.Sc, Das, Sushmita, Ph.D, Lal, Chandrashekhar, Ph.D, Pandey, Krishna, M.D, Das, Vidyanand R., M.B.B.S, Das, Pradeep, Ph.D
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; CD11b Antigen - metabolism; Chemokine CCL3 - metabolism; Chemokines; Cytokines; Cytokines - metabolism; Down-Regulation; Endothelial Cells; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; Human protozoal diseases; Human visceral leishmaniasis; Humans; Immunity, Innate; India; Infectious diseases; Innate immunity; Integrins; Interferon-gamma - metabolism; Interleukins - metabolism; L-Selectin - metabolism; Leishmania donovani; Leishmania donovani - immunology; Leishmaniasis, Visceral - complications; Leishmaniasis, Visceral - immunology; Leishmaniasis, Visceral - parasitology; Leshmaniasis; Malnutrition; Malnutrition - complications; Malnutrition - immunology; Medical sciences; Metabolic diseases; Monocytes; Monocytes - metabolism; Neutrophils - metabolism; Other nutritional diseases (malnutrition, nutritional and vitamin deficiencies...); Parasitic diseases; Phagocytosis; Polymorphonuclear cells; Protozoal diseases; Reactive Oxygen Species - metabolism; Transendothelial and Transepithelial Migration; Tumor Necrosis Factor-alpha - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2013.10.003

Abstract Objective Malnutrition may be significant in the modulation of immune responses in visceral leishmaniasis (VL). Data on the relationship between malnutrition and innate immune response in VL are limited. The aim of this study was to examine the effect of malnutrition on the profile of innate immune functions of polymorphonuclear neutrophil granulocytes (PMNs) and monocytes through comparison of well-nourished and malnourished Indian patients with VL. Methods Forty individuals were enrolled comprising 20 active and untreated cases of VL and 20 non-VL individuals from the endemic region of Bihar, India. The patients with VL were segregated into two groups of 10 well-nourished and 10 malnourished participants. Patients' blood samples were directed against a crude Leishmania donovani extract (soluble leishmanial antigen) and phorbol 12-myristate-13-acetate plus ionomycin. The transendothelial cell adherence migration abilities of the PMNs and monocytes directed against these antigens were determined in whole-blood assays by flow cytometry. The chemokine (interleukin [IL]-8, macrophage inflammatory protein [MIP]-1 α) and cytokine support (tumor necrosis factor -α, interferon [IFN]-γ, IL-10), which could be significant in transendothelial cell migration, and efficacies of antileishmanial phagocytic function and reactive oxygen species (ROS) generation were also determined. Results Severe hindrance in the adherence of innate immune cells to the endothelial wall due to Leishmania parasites, as revealed by decreased shedding of l -selectin (CD62 L) and down-regulation of CD11 b expression on the surface of the PMNs and monocytes, occurred in malnourished VL patients. The production of MIP-1 α and IL-8 in response to L. donovani antigen was reduced in malnourished patients. In contrast, malnutrition in VL patients significantly reduced the IFN-γ and TNF-α produced by these immune cells, whereas the levels of IL-10 were significantly elevated. Malnourished VL patients were observed with severely dysfunctional PMNs and monocytes in terms of ROS activity that could not be recovered by stimulation with L. donovani antigen. Conclusions Malnutrition linked to VL can be a decisive factor in the dynamics of L. donovani evasion of innate immune cell function in VL patients.