Modulatory effect of mannose-binding lectin on cytokine responses: possible roles in HIV infection.
BACKGROUND
Mannose-binding lectin (MBL) is a soluble receptor of the innate immune system, probably contributing to antimicrobial defence. The possible role of MBL in HIV infection is unclear.


METHODS
Peripheral blood mononuclear cells (PBMCs) from 28 HIV-infected patients and 13 healthy controls were stimulated with MBL and costimulated with HIV-1 gp120 or mannan from Saccharomyces cerevisiae before inflammatory responses in PBMC cultures were examined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. HIV-1 RNA replication in vitro was assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR) in supernatants from patients with measurable HIV-1 RNA levels.


RESULTS
(i) Enhanced TNF-alpha responses were observed when PBMCs from healthy controls and HIV-infected patients were stimulated with MBL and costimulated with HIV-1 gp120 or mannan. (ii) MBL stimulation induced increased HIV RNA replication in culture supernatants when costimulated with mannan.


CONCLUSIONS
The present study suggests a modulatory role of MBL on cytokine responses, and HIV replication after stimulation with microbial products. These effects of MBL on inflammatory responses and viral replication may be clinically relevant for HIV infection.
Heggelund
L
L
Section of Clinical Immunology and Infectious Diseases, Medical Department, Research Institute for Internal Medicine, Rikshospitalet University Hospital, University of Oslo, Oslo, Norway. lars.heggelund@medisin.uio.no
Mollnes
T E
TE
Espevik
T
T
Müller
F
F
Kristiansen
K I
KI
Aukrust
P
P
Frøland
S S
SS
D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008351:Mannans / Q000494:pharmacology; D037601:Mannose-Binding Lectin / Q000494:pharmacology*; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014779:Virus Replication
D015699:HIV Envelope Protein gp120; D008351:Mannans; D037601:Mannose-Binding Lectin; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha