MEM INST OSWALDO CRUZ, RIO DE JANEIRO, 112(4) April 2017
PAGES: 260-268 DOI: 10.1590/0074-02760160366 Full paper
Polymorphisms in genes TLR1, 2 and 4 are associated with differential cytokine and chemokine serum production in patients with leprosy

Nadja de Lima Santana2,3, Jamile Leão Rêgo2,3, Joyce Moura Oliveira2, Lucas Frederico de Almeida2, Marcos Braz2,3, Lídia Maria Medeiros Machado1, Paulo Roberto Lima Machado1,2,3, Léa Cristina Castellucci1,2,3,+

1Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Salvador, BA, Brasil
2Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, Serviço de Imunologia, Salvador, BA, Brasil
3Universidade Federal da Bahia, Programa de Pós-Graduação em Ciências da Saúde, Salvador, BA, Brasil

Abstract

BACKGROUND Leprosy or hansen’s disease is a spectral disease whose clinical forms mostly depends on host’s immune and genetic factors. Different Toll-like receptors (TLR) variants have been described associated with leprosy, but with some lack of replication across different populations.

OBJECTIVES To evaluate the role of polymorphisms in genes TLR1, TLR2 and TLR4 and susceptibility to leprosy in a genetic case control study; to verify the association between genotypes of these markers and the immunological profile in the serum of patients with leprosy.

METHODS Pre-designed TaqMan® assays were used to genotype markers at TLR1 (rs4833095, rs5743551), TLR2 (rs7656411, rs3804099) and TLR4 (rs1927914, rs1927911). A panel of cytokines and chemokines was accessed by enzime-linked immunosorbent assay (ELISA) test in the serum of a subgroup of patients with and without leprosy reactions.

FINDINGS Our results show an association between the T allele of rs3804099 at the TLR2 gene and increased risk for leprosy per se [Odds ratio (OR) = 1.296, p = 0,022]. In addition, evaluating the association between different genotypes of the TLR1, 2 and 4 markers and cytokine/chemokine serological levels, IL-17 appears as an immunological marker regulated by the polymorphism of the three TLR genes evaluated, whereas different TLR1 genotypes were associated with differential production of IL-12p40 and MCP-1(CCL2). Furthermore, other relevant serum markers such as CXCL-10 and IL-6 seemed to be regulated by TLR2 variants and IL-1β was related to TLR4 genotypes.

MAIN CONCLUSIONS All together our data points that the tested TLR markers may have a regulatory role in the immunity against Mycobacterium leprae, by driving the host’s production of key cytokines and chemokines involved in the pathogenesis of this disease.

Financial support: INCT-DT (Nº 573839/2008-5).
+ Corresponding author: This e-mail address is being protected from spambots. You need JavaScript enabled to view it.
Received 12 August 2016
Accepted 23 December 2016

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