Vaccine-induced protection against Leishmania amazonensis is obtained in the absence of IL-12/23p40.
Protozoa of the genus Leishmania are intracellular parasites of macrophages and may cause diverse clinical forms of leishmaniasis, including cutaneous, diffuse cutaneous, mucocutaneous and visceral leishmaniasis. Infection with L. major in mice indicates that a protective immune response is achieved when Th1 cells are developed. Thus, adoptive or vaccine-induced protection against leishmaniasis is largely dependent on cell-mediated immunity and IFN-gamma production. Induction of a Th1 response is dependent on the presence of IL-12 whilst lymphocytes are activated. This study was aimed at evaluating the role of IL-12 during infection with L. amazonensis and after vaccination with Leishvacin (killed Leishmania amazonensis promastigotes), since the role of this cytokine in vaccine-induced immunity with this preparation in experimental models or in humans is not yet elucidated. Hence, C57BL/6 interleukin-12-deficient mice (IL-12p40(-/-)) and wild-type controls (wt) were infected with L. amazonensis and the course of infection, parasite burden and cytokine production were compared. IL-12p40(-/-) mice were more susceptible to L. amazonensis than wt: lesions and parasite burden were larger in IL-12p40(-/-) when compared to wt. Interestingly, IL-4 was not produced in the absence of IL-12 in response to infection with L. amazonensis. To evaluate the role of IL-12 in the vaccine-induced immunity against L. amazonensis infection, IL-12p40(-/-) wt mice were vaccinated in the base of the tail and subsequently challenged with L. amazonensis in the footpads. Surprisingly, vaccinated IL-12p40(-/-) mice developed smaller lesions and had fewer parasites in footpads than non-vaccinated controls. Lymph node and spleen cells from vaccinated IL-12p40(-/-) mice did not produce high levels of IFN-gamma in response do in vitro stimulus with antigen. Hence, partial protection against infection with L. amazonensis could be obtained in the absence of functional IL-12 and a typical Th1 response.
Hernández
Mayra Xiomara
MX
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas/ICB, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
Barçante
Thales Augusto
TA
Vilela
Luciano
L
Tafuri
Wagner Luiz
WL
Afonso
Luís Carlos Crocco
LC
Vieira
Leda Quercia
LQ
D000818:Animals; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000172:deficiency* / Q000235:genetics; D053762:Interleukin-12 Subunit p40; D015847:Interleukin-4 / Q000096:biosynthesis; D007894:Leishmania mexicana / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021122:Protein Subunits / Q000172:deficiency* / Q000235:genetics; D016052:Protozoan Vaccines / Q000494:pharmacology*
D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D016052:Protozoan Vaccines; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma