Local and systemic immune response to inactivated C. albicans in mice

Abstract To improve our understanding of the role natural-immunity cells play in regulating the immune response to Candida albicans (CA) we compared local versus systemic effects of intraperitoneal inoculations with inactivated CA cells in mice. Peritoneal exudate cells (PECs) and spleen cells (SCs) were recovered from CD2F1 mice after 5 intraperitoneal CA injections (2 x 10(7) cells/mouse on days -14, -10, -7, -3 and 0 (CA-5d) with respect to in vitro assays performed at 2 h, 24 h, 3 days and 5 days). Northern blot analysis revealed that 2 h after CA-5d, PECs expressed a high level of IL-2, IFN-gamma, IL-1 beta and a low level of IL-10 and TNF-alpha mRNAs, while IL-4 and IL-5 mRNAs were absent, suggesting the development of TH1 subset. At 24 h, while IL-2 mRNA remained high, IL-1 beta and IFN-gamma expression had decreased and IL-10 and TNF-alpha mRNAs were no longer detectable. Instead, in spleens of CA-treated mice, examined up to 5 days after CA-5d, only IL-2 and IL-1 beta mRNAs were detectable, but the expression level was similar to that of untreated control mice. CA-5d induced a high level of natural-killer (NK)/lymphokine-activated-killer (LAK) activity in the peritoneal cavity but did not affect spleen NK activity. After CA-5d, the proliferative response of PECs to mitogens and CA antigens was also different from that of SCs. Unfractionated PECs were unable to proliferate in response to concanavalin A (Con A), IL-2, CA cells and CA cell wall mannoprotein, but after removal of the nylon-wool-adherent fraction, the nonadherent peritoneal cells (Nad-PECs) showed a significant proliferative response to mitogens. After depletion of NK cells by anti-asialo-GM1 antibody plus complement, the proliferative response of Nad-PECs to Con A and CA increased further. Contrary to the PEC response, unfractionated SCs from the same animals responded very well to mitogens and CA antigens and the proliferative response was significantly higher compared to that of SC from control mice. In conclusion, these results cast some light on the mechanisms by which NK cells and macrophages regulated the development of the local specific response to CA: activated NK cells, by producing IFN-gamma, favor the development of TH1 subset, while suppressor macrophages keep proliferation of T lymphocytes under control because of the presence of highly activated NK cells.