Enhancement of HIV-1 replication in peripheral blood mononuclear cells by Cryptococcus neoformans is monocyte-dependent but tumour necrosis factor-independent.
OBJECTIVE
To investigate the possible role of Cryptococcus neoformans in HIV-1 pathogenesis.


METHODS
An in vitro system was developed to study HIV-1 replication in freshly HIV-1-infected peripheral blood mononuclear cells (PBMC) incubated with whole azide-killed C. neoformans.


METHODS
Human PBMC or peripheral blood lymphocytes were infected with lymphocytotropic HIV-1 and incubated with azide-killed encapsulated or non-encapsulated C. neoformans for 10 days. Viral replication was followed by HIV-1 p24 enzyme-linked immunosorbent assay and median tissue culture infective dose determination. Tumour necrosis factor (TNF) release by PBMC, induced by C. neoformans, was measured. Anti-TNF monoclonal antibodies or pentoxifylline were used to inhibit TNF bioactivity.


RESULTS
Both encapsulated and non-encapsulated C. neoformans enhanced HIV-1 replication in PBMC but not in peripheral blood lymphocytes. C. neoformans induced TNF release by PBMC. Inhibition of TNF bioactivity did not block C. neoformans-enhanced HIV-1 replication in PBMC.


CONCLUSIONS
C. neoformans can enhance HIV-1 replication in T cells only in the presence of monocytic cells. This enhancement is not dependent on encapsulation nor can it be attributed to TNF release.
Orendi
J M
JM
Department of Clinical Microbiology, University Hospital Utrecht, The Netherlands.
Nottet
H S
HS
Visser
M R
MR
Verheul
A F
AF
Snippe
H
H
Verhoef
J
J
D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D003455:Cryptococcus neoformans / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000382:microbiology* / Q000502:physiology; D010431:Pentoxifylline / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline