Up-regulation of T helper 2 and down-regulation of T helper 1 cytokines during murine retrovirus-induced immunodeficiency syndrome enhances susceptibility of a resistant mouse strain to Leishmania amazonensis.
Resistance to and recovery from leishmania infection is dependent on cell-mediated immunity. C57BL/6 mice are resistant to Leishmania amazonensis (La) infection but susceptible to LP-BM5 murine leukemia virus (MuLV) infection. MuLV infection leads to a state of immunodeficiency characterized by severe compromise of cell-mediated immunity. When infected with La alone, C57BL/6 mice developed a small transient lesion that evolved to spontaneous healing or a lesion with extremely slow growth. Lesions were predominantly comprised of a lympho-macrophagic infiltrate with few parasitized macrophages. When infected with La and, 4 weeks later, with MuLV (La-MuLV), the mice developed a large uncontrolled nonhealing lesion containing vacuolated and heavily parasitized macrophages. In contrast, mice infected with MuLV first and La 4 weeks later (MuLV-La) developed a small but persistent lesion, characterized histologically by a small number of heavily parasitized macrophages and few lymphocytes. Eight weeks after MuLV infection, both had similar immunological profiles with decreased lymphocyte proliferation, diminished production of interferon-gamma, and high production of interleukins 4 and 10. At the time of L. amazonensis infection, La-MuLV animals have a normal T cell function whereas in MuLV-La mice this function is already impaired; this may influence the recruitment of macrophages to the site of leishmania injection.
Barral-Netto
M
M
School of Medicine, Federal University of Bahia, Brazil.
da Silva
J S
JS
Barral
A
A
Reed
S
S
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004198:Disease Susceptibility / Q000209:etiology; D005260:Female; D020022:Genetic Predisposition to Disease; D007896:Leishmaniasis / Q000209:etiology* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D012192:Retroviridae Infections / Q000150:complications* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*
D016207:Cytokines