Immunization of BALB/c mice with mIFN-gamma-secreting Mycobacterium bovis BCG provides early protection against Leishmania major infection.
We developed and tested IFN-gamma-expressing Mycobacterium bovis, strain BCG, for the ability to activate macrophages and protect mice against a heterologous challenge with Leishmania major. One, 2 or 3 weeks after intraperitoneal immunization, mice were challenged with 10(6) L. major amastigotes injected into the right footpad. Recombinant BCG immunization for all 3 challenge time points initially showed greater protection compared to the BCG control, as judged by footpad thickness and number of parasites in the leishmanial lesion. However, at week 4 after challenge, while the 1- and 2-week immunization groups continued to show increased protection, the 3-week immunization group animals exhibited progressive disease. These data suggest that the IFN-gamma-expressing BCG initially activates macrophages more effectively than native BCG, but that late exacerbation of disease can occur, highlighting the complexity of the immune response against leishmaniasis.
Kong
D
D
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
Belosevic
M
M
Kunimoto
D Y
DY
D000818:Animals; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D007114:Immunization; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control*; D008262:Macrophage Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
D001500:BCG Vaccine; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D007371:Interferon-gamma