Association of CD209 (DC-SIGN) rs735240 SNV with paucibacillary leprosy in the Brazilian population and its functional effects

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Giovanna Valle Germano ; André Flores Braga ; Rodrigo Mendes de Camargo ; Priscila Betoni Ballalai ^[4] ; Ohanna Cavalcanti Bezerra ^[5] ; Fernanda Saloum de Neves Manta ^[6] ; Andréa de Faria Fernandes Belone ^[7] ; Cleverson Teixeira Soares ^[8] ; Pranab Kumar Das ^[9] ; Milton Ozório Moraes ^[10] ; Ana Carla Pereira Latini ^[11] ; Vânia Niéto Brito de Souza ^[12]

• Tipo de documento: Artigo Científico
• Fonte: Memórias do Instituto Oswaldo Cruz; v. 117, 2022-06-10.

Resumo

BACKGROUND Leprosy, caused by Mycobacterium leprae, is a public health problem in Brazil that affects peripheral nerves, resulting in physical disabilities. During host-pathogen interactions, the immune response determines leprosy outcomes from a localised (paucibacillary) form to a disseminated (multibacillary) form. The recognition of M. leprae involves the DC-SIGN receptor, which is present on the dendritic cells (DCs) and participates in immune activation. OBJECTIVES To evaluate the association of polymorphisms in the promoter region of the gene encoding DC-SIGN (CD209) and the clinical form of leprosy, and to investigate its functional effects. METHODS The study population included 406 leprosy patients from an endemic area in Brazil [310 multibacillary (MB); 96 paucibacillary (PB)]. A functional evaluation based on the effects of the single nucleotide variant (SNV) associated with PB leprosy on the specific immune response was also performed. RESULTS The GA genotype and the presence of the A allele of rs735240 (-939G>A) were associated with PB leprosy [OR: 2.09 (1.18-3.69) and 1.84 (1.07-3.14), respectively]. Carriers of the A allele showed reduced expression of CD209 and TGF-β1 in leprosy lesions in comparison with individuals with GG genotype, in addition to a higher response to the Mitsuda test. CONCLUSION These data suggest that rs735240 influences the immune response against M. leprae and clinical presentation of leprosy. (AU)

• Processo FAPESP: 09/01436-1 - Estudo da maturação de células dendríticas na hanseníase
• Beneficiário: Vânia Nieto Brito de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular