IL-10 leads to a higher parasite persistence in a resistant mouse model of Leishmania major infection.
IL-10 is a cytokine secreted by a wide variety of cell types and has pleiotropic activities, mainly as a modulator of the immune response. In this study, we tested in a direct way the influence of IL-10 expression on Leishmania major infection in resistant mice. We report that C57BL/6 mice treated with a single inoculation of recombinant adenovirus vector-expressing viral IL-10 (Ad-vIL-10), 1 day before parasitic challenge, exhibited a dual effect on footpad swelling, characterized by a decrease on lesion size at the early stage of the infection, followed by a rapid increase of these lesions that attained the complete healing later in infection. The reduction in lesion swelling in vIL-10 treated mice was accompanied by a decrease cellular infiltration of lymphocytes and monocytes at the site of parasite inoculation. Most significantly, vIL-10 administration led to a higher parasite burden in the draining popliteal lymph nodes late during infection, when the complete healing of the lesions was already achieved. RT-PCR analysis showed no important modification of cytokine transcripts in vIL-10 treated mice, early in infection, indicating no changes in mouse phenotype from resistant to susceptible status. Therefore, IL-10 administration influenced the outcome of the disease by modifying the inflammation and local cell recruitment at the site of parasite penetration and by leading to an enhanced residual parasite load in popliteal lymph nodes later in infection. The implication of IL-10 on the host immune status and the establishment and outcome of the infection is discussed.
Viana da Costa
Alexandra
A
UMR-CNRS 8527, Institut Pasteur de Lille-Institut de Biologie de Lille, 1 rue Professeur A. Calmette, 59021 Lille, France. monica.vianadacosta@ibl.fr
Huerre
Michel
M
Delacre
Myriam
M
Auriault
Claude
C
Correia Costa
José Manuel
JM
Verwaerde
Claudie
C
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D007111:Immunity, Cellular; D007113:Immunity, Innate / Q000276:immunology; D007249:Inflammation / Q000209:etiology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics*; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma