title: Leishmania donovani: dynamics of L. donovani evasion of innate immune cell attack due to malnutrition in visceral leishmaniasis.
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.
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences, Bihar, India.
authors.forename: Vikash
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences, Bihar, India. Electronic address: Drsbimal24@yahoo.com.
authors.forename: Sanjiva
authors.initials: S
authors.lastname: Bimal
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences, Bihar, India.
authors.forename: Shubhankar K
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences, Bihar, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Chaudhary
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences, Bihar, India.
authors.forename: Sushmita
authors.initials: S
authors.lastname: Das
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences, Bihar, India.
authors.forename: Chandrashekhar
authors.initials: C
authors.lastname: Lal
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences, Bihar, India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Pandey
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences, Bihar, India.
authors.forename: Vidyanand R
authors.initials: VR
authors.lastname: Das
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences, Bihar, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Das
mesh_terms: D039481:CD11b Antigen / Q000378:metabolism; D054405:Chemokine CCL3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D042783:Endothelial Cells; D006801:Humans; D007113:Immunity, Innate; D007194:India; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000150:complications* / Q000276:immunology / Q000469:parasitology; D044342:Malnutrition / Q000150:complications* / Q000276:immunology; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D054405:Chemokine CCL3; D016207:Cytokines; D007378:Interleukins; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D007371:Interferon-gamma
keywords: Chemokines; Cytokines; Human visceral leishmaniasis; Innate immunity; Integrins; Malnutrition; Monocytes; Polymorphonuclear cells