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.
Department of Clinical Microbiology, University Hospital Utrecht, The Netherlands.
J M
JM
Orendi
H S
HS
Nottet
M R
MR
Visser
A F
AF
Verheul
H
H
Snippe
J
J
Verhoef
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