Role of CD4+ T cells in a protective immune response against Cryptococcus neoformans in the central nervous system.
Cryptococcosis is a life-threatening disease caused by the encapsulated yeast, Cryptococcus neoformans. Although infection with C. neoformans is initiated in the lungs, morbidity and mortality is mostly associated with infections of the central nervous system (CNS). Individuals with deficiencies in cell-mediated immunity, such as patients with AIDS, are more susceptible to disseminated cryptococcosis, highlighting the importance of cell-mediated immunity and CD4+ T cells in host resistance against C. neoformans. Using a mouse model of cryptococcal meningoencephalitis, we have shown that immunization of mice with a cryptococcal antigen induced a protective immune response that crossed the blood-brain barrier and initiated an immune response directly in the CNS if C. neoformans was present. The regional protective response was characteristic of a Type-1 (Th1) response in the types of cells present at the site of infection and in the cytokines and chemokines expressed. Here, we extend those findings and report that CD4+ T cells are required for survival of immune mice infected directly in the brain with C. neoformans and sensitized CD4 + T cells can transfer partial protection to naive mice infected intracerebrally with C. neoformans. Furthermore, CD4 + T cells were also important for optimal infiltration of inflammatory cells at the site of infection and in the expression of cytokines and chemokines associated with protection in the brain. Lastly, CD4+ T cells were required for optimal regional production and secretion of IFNgamma and in the significantly increased expression of iNOS in C. neoformans-infected brains of immune mice.
Uicker
William C
WC
Program in Molecular Pathogenesis and Immunity, Department of Dermatology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA.
McCracken
James P
JP
Buchanan
Kent L
KL
D019264:Adoptive Transfer; D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018925:Chemokines / Q000032:analysis; D015169:Colony Count, Microbial; D003455:Cryptococcus neoformans / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis; D016919:Meningitis, Cryptococcal / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D008856:Microscopy, Fluorescence; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D016019:Survival Analysis
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse