IL-15 in human visceral leishmaniasis caused by Leishmania infantum.
Interleukin (IL)-15 is a recently discovered cytokine with the ability to stimulate the proliferation activity of Th1 and/or Th2 lymphocytes. Here, we investigated the involvement of IL-15 in the immune response to Leishmania infantum infection by studying patients with visceral leishmaniasis (VL). We found that IL-15 is produced by leishmanial antigen (LAg)-stimulated peripheral blood mononuclear cells (PBMC) from active VL patients at a significantly higher level than those produced by cells from healed VL subjects or healthy controls. A significant increase in IL-15 serum blood levels was also observed in acute VL patients compared with healed ones. Furthermore, recombinant IL-15 had an appreciable effect in vitro in reducing IL-4 and increasing the production of IL-12 in response to LAg, but it was ineffective in altering the production of interferon-gamma (IFN-gamma). The production of endogenous IL-15 in acute VL patients appeared to be insufficient to activate both IFN-gamma and IL-12, as attested by the absence of modification of these two cytokines by neutralization experiments in the presence of anti-IL-15 monoclonal antibodies (MoAB). On the contrary, the neutralization of IL-15 increased IL-4 production. Together, these results indicate that endogenous IL-15 plays a role in the suppression of Th2-type cytokines, even though it does not enhance the production of Th1 cytokines in acute VL patients. Since IL-15, in the presence of anti-IL-4 MoAb, caused a further increase in IL-12 production and led to a significant production of IFN-gamma, one of its indirect effects on Th1 cell activation could be due to the latter's effect on Th2 cytokines such as IL-4. Therefore, our observations indicate that there is a potential for IL-15 to augment the T-cell response to human intracellular pathogens.
Milano
S
S
Department of Biopathology and Biomedical Methodologies, University of Palermo, Italy.
Di Bella
G
G
D'Agostino
P
P
Barbera
C
C
Caruso
R
R
La Rosa
M
M
Ferlazzo
V
V
Vitale
G
G
La Russa
C
C
Gambino
G
G
Chifari
N
N
Mansueto
S
S
Cillari
E
E
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000953:Antigens, Protozoan / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism; D019409:Interleukin-15 / Q000097:blood / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D018314:Leishmania infantum / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000097:blood / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D019409:Interleukin-15; D011994:Recombinant Proteins; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma