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Early induction of interleukin-12 by human monocytes exposed to Cryptococcus neoformans mannoproteins
L Pitzurra1, R Cherniak, M Giammarioli
1Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06122 Perugia, Italy.
Abstract:
Interleukin-12 (IL-12) production by human monocytes stimulated with mannoproteins (MPs) of Cryptococcus neoformans was investigated. The results reported show that secreted or cell-associated MPs induce an early and significant production of IL-12. MPs show different capabilities to quantitatively affect IL-12 production; MP2, an 8. 2-kDa MP purified from the culture supernatant of C. neoformans, appears to be the most potent stimulator. Cytochalasin B inhibits both internalization and IL-12 induction by MP. In addition, a drastic reduction of IL-12 was observed when monocytes were cultured in the absence of normal human serum or treated with soluble mannan. Early production of IL-12 promotes early secretion of gamma interferon by T cells but does not influence the magnitude of the MP-induced lymphoproliferative response. Overall our results identify cryptococcal antigens responsible for rapid and potent induction of IL-12 in monocytes. MPs appear to regulate IL-12 secretion by internalization via the endocytic pathway and by interaction with monocyte receptors or serum factors.
Insights
Mannoproteins (MPs) from Cryptococcus neoformans stimulate human monocytes to produce Interleukin-12 (IL-12). Specific MPs, like MP2, are potent stimulators, with induction dependent on internalization and serum factors.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Cryptococcus neoformans is an opportunistic fungal pathogen.
- Monocytes play a crucial role in the innate immune response.
- Interleukin-12 (IL-12) is a key cytokine in cell-mediated immunity.
Purpose of the Study:
- To investigate the role of Cryptococcus neoformans mannoproteins (MPs) in stimulating Interleukin-12 (IL-12) production by human monocytes.
- To identify specific MPs responsible for IL-12 induction.
- To elucidate the mechanisms underlying MP-induced IL-12 production.
Main Methods:
- Human monocytes were stimulated with various mannoproteins (MPs) from Cryptococcus neoformans.
- IL-12 production was quantified.
- The effect of cytochalasin B, normal human serum, and soluble mannan on IL-12 induction was assessed.
- Gamma interferon secretion by T cells was measured.
Main Results:
- Secreted and cell-associated MPs induced significant early production of IL-12.
- MP2, an 8.2-kDa MP, was identified as the most potent stimulator of IL-12.
- MP internalization and IL-12 induction were inhibited by cytochalasin B.
- IL-12 production was reduced in the absence of normal human serum or with soluble mannan treatment.
- Early IL-12 production promoted early gamma interferon secretion but did not affect lymphoproliferation.
Conclusions:
- Cryptococcal mannoproteins are potent inducers of IL-12 production in human monocytes.
- MP-induced IL-12 secretion is regulated by internalization via the endocytic pathway and interactions with monocyte receptors or serum factors.
- Early IL-12 induction by MPs influences subsequent T cell responses.