Polymorphisms in genes TLR1, 2 and 4 are associated with differential cytokine and chemokine serum production in patients with leprosy.
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.


OBJECTIVE
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.


RESULTS
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.


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.
Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, Serviço de Imunologia, Salvador, BA, Brasil.|Universidade Federal da Bahia, Programa de Pós-Graduação em Ciências da Saúde, Salvador, BA, Brasil.
Nadja de Lima
NL
Santana
Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, Serviço de Imunologia, Salvador, BA, Brasil.|Universidade Federal da Bahia, Programa de Pós-Graduação em Ciências da Saúde, Salvador, BA, Brasil.
Jamile Leão
JL
Rêgo
Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, Serviço de Imunologia, Salvador, BA, Brasil.
Joyce Moura
JM
Oliveira
Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, Serviço de Imunologia, Salvador, BA, Brasil.
Lucas Frederico de
LF
Almeida
Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, Serviço de Imunologia, Salvador, BA, Brasil.|Universidade Federal da Bahia, Programa de Pós-Graduação em Ciências da Saúde, Salvador, BA, Brasil.
Marcos
M
Braz
Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Salvador, BA, Brasil.
Lídia Maria Medeiros
LM
Machado
Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Salvador, BA, Brasil.|Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, Serviço de Imunologia, Salvador, BA, Brasil.|Universidade Federal da Bahia, Programa de Pós-Graduação em Ciências da Saúde, Salvador, BA, Brasil.
Paulo Roberto Lima
PR
Machado
Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Salvador, BA, Brasil.|Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, Serviço de Imunologia, Salvador, BA, Brasil.|Universidade Federal da Bahia, Programa de Pós-Graduação em Ciências da Saúde, Salvador, BA, Brasil.
Léa Cristina
LC
Castellucci
D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood* / Q000276:immunology; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005838:Genotype; D006801:Humans; D007918:Leprosy / Q000235:genetics* / Q000276:immunology*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D051194:Toll-Like Receptor 1 / Q000235:genetics*; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D055815:Young Adult
D018925:Chemokines; D016207:Cytokines; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4