Immune response to LinB13, a Lutzomyia intermedia salivary protein correlates with disease severity in tegumentary leishmaniasis

(1)Instituto Gonçalo Moniz, FIOCRUZ, Salvador, Bahia, Brazil.

(2)Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Salvador, Bahia, Brazil.

(3)Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.

(4)Immunology Service of the University Hospital Professor Edgard Santos, Federal University of Bahia, Salvador, Bahia, Brazil.

BACKGROUND: We have previously shown that seropositivity to rLinB-13, a salivary protein from Lutzomyia intermedia, predicted sand fly exposure and was associated with increased risk of developing cutaneous leishmaniasis (CL). METHODS: Herein, we investigated the cellular immune response to saliva from Lu. intermedia, using rLinB-13 as a surrogate antigen in naturally exposed individuals presenting positive serology to LinB-13. We also investigated the response to rLinB-13 in leishmaniasis patients, displaying active ulcers and positive PCR for L. braziliensis. RESULTS: Peripheral blood mononuclear cells (PBMCs) stimulated in vitro with rLinB-13 secreted elevated levels of IL-10, IL-4, IL-1β, IL-1α, IL-6 and chemokines (CCL3, CCL4, CCL5 and CXCL5). CL, and disseminated leishmaniasis (DL) patients displayed a significantly higher IgG response to rLinB-13, compared to healthy subjects and anti-rLinB-13 IgG was positively correlated with the number of lesions in DL patients. Positive serology to rLinB-13 was also associated with chemotherapy failure. PBMCs from DL patients stimulated with rLINB-13 secreted significantly higher levels IL-10 and IL-1β compared to CL individuals. CONCLUSIONS: In this study, we observed an association between humoral and cellular immune response to the sand fly salivary protein rLinB-13 and disease severity in tegumentary leishmaniasis. This study brings evidence that immunity to rLinB-13 influences disease outcome in L. braziliensis infection and results indicate that positive serology to rLinB-13 IgG can be employed as marker of DL, an emerging and severe form of disease caused by L. braziliensis.