Effects of essential fatty acid deficiency on prostaglandin E2 production and cell-mediated immunity in a mouse model of leprosy.
Results from animal and in vitro studies suggest that essential fatty acid (EFA) deficiency enhances cell-mediated immunity by reducing production of prostaglandins with immunosuppressive actions. However, direct experimental evidence that EFA deficiency enhances T-lymphocyte function in vivo has not been obtained. In this study, athymic (nu/nu) mice were infected in the footpads with Mycobacterium leprae and fed a linoleic acid-free diet. These mice, and infected nu/nu mice on control diets, were given an adoptive transfer of M. leprae-primed, T-cell-enriched lymphocytes. After 2 weeks, M. leprae bacilli were harvested from the recipient mice and bacterial viability was determined by the BACTEC system. M. leprae recovered from recipient mice fed control diets displayed little reduction in metabolic activity. In contrast, M. leprae from recipient mice fed the EFA-deficient (EFAD) diet exhibited markedly reduced viability. In vitro, donor cells from M. leprae-primed mice secreted elevated levels of gamma interferon upon exposure to the bacilli. These cells also exhibited an enhanced proliferative response, which was reduced by exogenous prostaglandin E2 (PGE2). In addition, M. leprae-infected granuloma macrophages (Mphi) from EFAD recipient nu/nu mice secreted significantly less PGE2 than granuloma Mphi from mice on control diets. These data suggest that enhanced levels of Mphi-generated PGE2, induced by M. leprae or its constituents, could act as an endogenous negative modulator of the immune response occurring in the microenvironment of the lepromatous granuloma.
Adams
L B
LB
Gillis W. Long Hansen's Disease Center Laboratory Research Branch at Louisiana State University, Baton Rouge 70894, USA. ADAMS_L@vt8200.vetmed.Isu.edu
Gillis
T P
TP
Hwang
D H
DH
Krahenbuhl
J L
JL
D000818:Animals; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism*; D007111:Immunity, Cellular; D007918:Leprosy / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009166:Mycobacterium leprae; D013601:T-Lymphocytes / Q000276:immunology*
D005227:Fatty Acids; D015232:Dinoprostone