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

• Published in: Memórias do Instituto Oswaldo Cruz Vol. 112; no. 4
• Main Authors: Santana, Nadja de Lima, Rêgo, Jamile Leão, Oliveira, Joyce Moura, Almeida, Lucas Frederico de, Braz, Marcos, Machado, Lídia Maria Medeiros, Machado, Paulo Roberto Lima, Castellucci, Léa Cristina
• Format: Journal Article
• Language: English
• Published: Fundação Oswaldo Cruz, Fiocruz 22-10-2018
• Subjects: cytokine and chemokine serum production; leprosy; polymorphism analysis; TLR
• ISSN: 1678-8060

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.