title: Interleukin 10-Dominant Immune Response and Increased Risk of Cutaneous Leishmaniasis After Natural Exposure to Lutzomyia intermedia Sand Flies.
abstract: BACKGROUND
  Leishmaniasis is caused by parasites transmitted to the vertebrate host by infected sand flies. During transmission, the vertebrate host is also inoculated with sand fly saliva, which exerts powerful immunomodulatory effects on the host's immune response.
  
  
  METHODS
  We conducted a prospective cohort analysis to characterize the human immune response to Lutzomyia intermedia saliva in 264 individuals, from an area for cutaneous leishmaniasis (CL) caused by Leishmania braziliensis.
  
  
  RESULTS
  Antibodies were found in 150 individuals (56.8%); immunoglobulin G1 and G4 were the predominant subclasses. Recall responses to salivary gland sonicate showed elevated production of interleukin 10 (IL-10), interleukin 13, interferon γ, CXCL9, and CCL2 compared with controls. CD4(+)CD25(+) T cells, including Foxp3(+) cells, were the main source of IL-10. L. braziliensis replication was increased (P < .05) in macrophages cocultured with saliva-stimulated lymphocytes from exposed individuals and addition of anti-IL-10 reverted this effect. Positive correlation between antibody response to saliva and cellular response to Leishmania was not found. Importantly, individuals seropositive to saliva are 2.1 times more likely to develop CL (relative risk, 2.1; 95% confidence interval, 1.07-4.2; P < .05).
  
  
  CONCLUSIONS
  Exposure to L. intermedia sand flies skews the human immune response, facilitating L. braziliensis survival in vitro, and increases the risk of developing CL.
authors.affiliation: Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz.
authors.forename: Augusto M
authors.initials: AM
authors.lastname: Carvalho
authors.affiliation: Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz.
authors.forename: Juqueline R
authors.initials: JR
authors.lastname: Cristal
authors.affiliation: Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia.
authors.forename: Aline C
authors.initials: AC
authors.lastname: Muniz
authors.affiliation: Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais.
authors.forename: Lucas P
authors.initials: LP
authors.lastname: Carvalho
authors.affiliation: Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz.
authors.forename: Regis
authors.initials: R
authors.lastname: Gomes
authors.affiliation: Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz.
authors.forename: José C
authors.initials: JC
authors.lastname: Miranda
authors.affiliation: Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz Instituto de Investigação em Imunologia, Salvador, Bahia, Brazil.
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.affiliation: Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais.
authors.forename: Edgar M
authors.initials: EM
authors.lastname: Carvalho
authors.affiliation: Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz Instituto de Investigação em Imunologia, Salvador, Bahia, Brazil.
authors.forename: Camila I
authors.initials: CI
authors.lastname: de Oliveira
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000906:Antibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016753:Interleukin-10 / Q000378:metabolism*; D007892:Leishmania braziliensis / Q000302:isolation & purification*; D016773:Leishmaniasis, Cutaneous / Q000453:epidemiology* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011576:Psychodidae / Q000276:immunology*; D018570:Risk Assessment; D012463:Saliva / Q000276:immunology; D055815:Young Adult
chemical_list: D000906:Antibodies; D016207:Cytokines; D007074:Immunoglobulin G; D016753:Interleukin-10
keywords: ELISA; L. braziliensis; chemokines; cutaneous leishmaniasis; cytokines; killing assay; lutzomyia intermedia; sand fly saliva