Rapid clearance of Candida albicans mannan antigens by liver and spleen in contrast to prolonged circulation of Cryptococcus neoformans antigens

Abstract

Clearances of mannan antigen from Candida albicans and glucuronoxylomannan antigen from Cryptococcus neoformans were examined in nonimmune rabbits by using self-prepared latex agglutination tests. Injected intravenously, 20 mg of Candida mannan antigen was cleared from the serum with a half-life of approximately 2 h. In contrast, 20 ,ug of Cryptococcus glucuronoxylomannan antigen had a half-life in serum of approximately 24 h. At the latest, 9 h after injection, both antigens were no longer detectable without pretreatment of serum samples with protease and heating to 100°C, thus indicating rapid binding by serum proteins other than immunoglobulins. Candida mannan antigen clearance was also examined in nonimmune mice after intravenous injection of (i) 200 ,ug of Candida mannan antigen, which accumulated in the liver and spleen and persisted for 97 days; (ii) 2 x 107 ethanol-killed Candida blastospores, which was accompanied by rapid clearance of mannan from the blood but accumulation of mannan in the liver and spleen and slow clearance from these organs; (iii) 6 x 106 viable C. albicans cells (lethal infection), which resulted in a rapid decrease of Candida CFU in the blood, liver, and spleen during the first 8 h, after which blood cultures were negative on day 2 and viable Candida burdens in the liver and spleen persisted at 105 CFU/g, whereas Candida mannan antigen continued to circulate in the bloodstream and accumulated in the liver and spleen.

Rapid spread of mannan to the immune system, skin and joints within 6 hours after local exposure

“…These latter results are similar to those presented herein. Furthermore, mannan has previously been shown to be filtered by the spleen and liver in various animals [28,29]. Binding of aCII antibodies to cartilage may contribute to an inflammatory environment in tissues expressing CII; such tissues include bone marrow and cartilaginous joints [30].…”

Intravenous injection of Candida-derived mannan results in elevated tumor necrosis factor alpha levels in serum

“…A number of mannan ligands are present in mammalian tissue (5,16,26,31). Since a portion of these ligands are free in the serum or on cells which do not produce TNF-␣, they may represent antagonists to CAM-induced TNF-␣ secretion by binding CAM in vivo and preventing it from interacting with ligands on responsive cells.…”

“…To stimulate the response in vivo, the competitive nonstimulatory ligands may have to be saturated so as to allow sufficient stimulation of the stimulatory ligands. A number of ligands that bind mannose polymers exist in vivo, evidenced by the rapid removal of mannan from circulation (16). We expect that these ligands include at least two types, those which facilitate the TNF-␣ response and those which by virtue of being nonstimulatory are antagonistic to the stimulatory process.…”

A novel monoclonal antibody recognizing β(1–3) glucans in intact cells of Candida and Cryptococcus

“…Some of these tests are commercially available, such as the Pastorex Candida test, which has high specificity but low sensitivity (11). It has been proposed that high antibody levels, such as those found against mannan in patients with candidiasis, may hamper the detection of mannan antigens b (12)(13)(14). The high detection limit and formation of mannan-antimannan antibody complexes with rapid clearance of mannan from the circulation may partly explain the low sensitivity of these tests (1,13,15).…”

“…It has been proposed that high antibody levels, such as those found against mannan in patients with candidiasis, may hamper the detection of mannan antigens b (12)(13)(14). The high detection limit and formation of mannan-antimannan antibody complexes with rapid clearance of mannan from the circulation may partly explain the low sensitivity of these tests (1,13,15). We found that anti-b glucan antibody levels in humans with deep Candida infections were relatively low and mainly of the IgG2 subclass type (12).…”