Role of IL-17 gene polymorphism in Indian kala-azar.

BACKGROUND & OBJECTIVES: Visceral leishmaniasis or kala-azar is a fatal protozoan disease caused by an obligate intracellular parasite, Leishmania donovani. Susceptibility, establishment of infection and severity of this disease depend upon many factors, but it is the host immune system that plays decisive role in disease progression. Keeping this view into consideration, we investigated the probable relationship between polymorphisms rs2275913 and rs8193036 in IL-17 gene, and its association as a risk factor for kala-azar in an endemic population of Assam, India. METHODS: A total of 209 subjects, 76 kala-azar cases (male: 46, female: 30, mean age ± SD: 34.60 ± 12.61) and 133 controls (male: 66, female: 67, mean age ± SD: 33.35 ± 14.48) were included in this study. We analysed the polymorphisms, rs2275913 and rs8193036 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The data were analysed using logistic regression analysis and SPSS software. RESULTS: The results revealed that the mutant rs8193036 TT genotype conferred 4.7-fold higher risk for kala-azar (p = 0.00991, OR = 4.72, 95% CI = 1.330-16.911). A significant difference was found between the allele frequencies of rs8193036 (p = 0.029, OR = 1.64, 95% CI = 1.04-2.57) when comparisons were done using the genetic models of association. When stratification analysis was done on the basis of active and past cases we found that during active infection rs2275913 A allele was significantly associated with increased risk of kala-azar (p = 0.016, OR = 3.95, 95% CI = 1.21-12.87). INTERPRETATION & CONCLUSION: The findings revealed that IL-17 genetic variant, rs8193036 is an independent risk factor for kala-azar infection and may contribute in pathogenesis of the disease. Further, rs2275913 polymorphism of IL-17 gene is associated with kala-azar during active infection.

Role of IL-21 in host pathogenesis in experimental visceral leishmaniasis.

Visceral leishmaniasis (VL) is a major global health problem but still remains one of the neglected tropical diseases. Currently available chemotherapeutics are associated with severe toxicity and increased drug resistance. There is a need to explore for novel therapeutic strategies that could modulate host immune responses or work in synergy with chemotherapy of VL. Therefore, understanding the host immunological changes that play a vital role in disease pathology is a prerequisite for designing any interventions. We have investigated the role of IL-21 during the course of Leishmania donovani infection and after drug treatment. BALB/c mice were used to investigate the mRNA levels of IL-21 during active Leishmania donovani infection and after treatment using real time polymerase chain reaction (RT-PCR). Mice were divided in four groups i.e. Control (Group A), Infected (Group B), Uninfected treated (Group C) and Infected treated (Group D). Animals of Group C and D were treated with Amphotericin B. IL-21 mRNA levels in the spleen were estimated on days 1, 3, 7, 14, 17, 21, 28, 35, 45 and 60 post infection and also during course of treatment. We found that IL-21 mRNA levels was significantly up-regulated in the infected group with a fourfold increase at D60 p.i. (p < 0.001) and it was decreased significantly after the treatment. Our results suggest that IL-21 mRNA is associated with pathogenesis of Leishmania donovani infection and that therapeutics designed to suppress IL-21 could provide promising antileishmanial activity.