Responsiveness of human polymorphonuclear cells (PMNL) to stimulation by a mannoprotein fraction (MP-F2) of Candida albicans; enhanced production of IL-6 and tumour necrosis factor-alpha (TNF-α) by MP-F2-stimulated PMNL from HIV-infected subjects

Abstract

IL‐1β, IL‐6, IL‐8 and TNF‐α production by PMNL from 21 HIV‐infected (HIV+), including 11 full‐blown AIDS, and 20 HIV‐uninfected (HIV−) subjects (matched for age and sex to HIV+ ones) was studied by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and ELISA. PMNL from both categories of subjects were strongly stimulated in their actual cytokine production by a mannoprotein fraction (MP‐F2) of Candida albicans, as well as by the bacterial lipopolysaccharide (LPS). These stimulatory effects were apparently due to increased cytokine gene expression and were substantially reversed by the physiological inhibitor IL‐10. However, PMNL from HIV+ subjects showed increased IL‐6 and TNF‐α gene expression and produced more IL‐6 and TNF‐α than PMNL from HIV− controls, under similar stimulation conditions. This difference could not be attributed to a given stage of HIV infection, any associated medication, or to a generalized increase of gene expression, as quantitatively similar β‐actin and IL‐1β transcripts were detected. Moreover, no significant difference in IL‐8 production by the PMNL from HIV+ and HIV− subjects was observed. Our studies suggest that PMNL from HIV+ subjects might add to other cellular sources of IL‐6 and TNF‐α (e.g. monocytes‐macrophages) in contributing to the cytokine‐dysregulated pattern typical of the HIV+ patient.

Candida albicansYeast and Germ Tube Forms Interfere Differently with Human Monocyte Differentiation into Dendritic Cells: a Novel Dimorphism-Dependent Mechanism To Escape the Host's Immune Response

“…Poly(A) ϩ RNA was extracted from 1 ϫ 10 6 cells by using a Micro-FastTrack 2.0 kit (Invitrogen, San Diego, Calif.) according to the manufacturer's instructions and was reverse transcribed as previously described (46). Aliquots of cDNA that yielded equivalent amounts of ␤-actin amplified products were used for semiquantitative evaluation of cytokine gene expression.…”

Candida and candidiasis in HIV-infected patients

“…In addition to lipopolysaccharide (LPS), we detected Candida cell wall components in serum of AIDS patients (unpublished results). Mannoproteins and b-glucan components of this fungus have also been reported to be good inducers of pro-inflammatory cytokines such as IL-1b, IL-6 and TNF-a not only from antigen-presenting cell and monocytes but also from PMN of HIV-positive patients [ [75][76][77][78]. Of interest, mannoprotein-stimulated neutrophils from HIV-positive patients, even at early stages of HIV infection, similar to LPS-stimulated neutrophils, produced more IL-6 and TNF-a than equally stimulated neutrophils from healthy uninfected controls [76].…”

Deletion of the Two-Component Histidine Kinase Gene ( CHK1 ) of Candida albicans Contributes to Enhanced Growth Inhibition and Killing by Human Neutrophils In Vitro

“…Human PMNs were isolated essentially as reported previously (17). The susceptibility of CAF2 and the strains mentioned above to PMNs was first measured by a growth inhibition assay, as already described (16).…”