Phenotypic and functional characterization of NK cells in human immune response against the dimorphic fungus Paracoccidioides brasiliensis.
Besides their role in fighting viral infection and tumor resistance, recent studies have shown that NK cells also participate in the immune response against other infectious diseases. The aim of this study was to characterize the possible role of NK cells in the immune response against Paracoccidioides brasiliensis. Purified NK cells from paracoccidioidomycosis patients and healthy individuals were incubated with P. brasiliensis yeast cells or P. brasiliensis-infected monocytes, with or without the addition of recombinant IL-15. We found that NK cells from paracoccidioidomycosis patients exhibit a lower cytotoxic response compared with healthy individuals. NK cells are able directly to recognize and kill P. brasiliensis yeast cells, and this activity seems to be granule-dependent but perforin-independent, whereas the cytotoxicity against P. brasiliensis-infected monocytes is perforin-dependent. These results indicate that NK cells participate actively in the immune response against the P. brasiliensis infection either by directly destroying yeast cells or by recognizing and killing infected cells. Granulysin is the possible mediator of the cytotoxic effect, as the reduced cytotoxic activity against the yeast cells detected in patients with paracoccidioidomycosis is accompanied by a significantly lower frequency of CD56(+)granulysin(+) cells compared with that in healthy controls. Furthermore, we show that NK cells released granulysin in cultures after being stimulated by P. brasiliensis, and this molecule is able to kill the yeast cells in a dose-dependent manner. Another important finding is that stimulated NK cells are able to produce proinflammatory cytokines (IFN-γ and TNF-α) supporting their immunomodulatory role in the infection.
Department of Clinical Pathology, State University of Campinas, Campinas, São Paulo, Brazil.
Larissa N A
LN
Longhi
Rosiane M
RM
da Silva
Márcia C
MC
Fornazim
Maria C
MC
Spago
Rômulo T D
RT
de Oliveira
Alexandre E
AE
Nowill
Maria H S L
MH
Blotta
Ronei L
RL
Mamoni
D000935:Antifungal Agents / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D018836:Inflammation Mediators / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology; D010228:Paracoccidioides / Q000276:immunology* / Q000472:pathogenicity; D010229:Paracoccidioidomycosis / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000935:Antifungal Agents; D000945:Antigens, Differentiation, T-Lymphocyte; C075005:GNLY protein, human; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma