Isolates of Candida albicans that differ in virulence for mice elicit strain-specific antibody-mediated protective responses

Abstract

Three distinct isolates of Candida albicans were used to establish systemic and oral infections in inbred mice that are genetically resistant or susceptible to tissue damage. Patterns of infection differed significantly between both yeasts and mouse strains. Systemic infection conferred significant protection against re-challenge with the homologous, but not the heterologous yeast; however, the protective effect was more evident in the tissue-susceptible CBA/CaH mice than in the resistant BALB/c strain. In contrast, oral infection induced protection against both homologous and heterologous oral challenge, although this was significant only in the CBA/CaH mice. CBA/CaH mice produced antibodies of both IgG1 and IgG2a subclasses, whereas BALB/c mice produced predominantly IgG1. Western blotting demonstrated considerable differences between epitopes recognised by serum antibodies from mice of both strains after immunisation with each of the three yeasts. Thus, different strains of yeast show considerable specificity in antibody responses elicited by either systemic or oral infection.

Effector function of leucocytes from susceptible and resistant mice against distinct isolates of Candida albicans

“…Although it has long been accepted that isolates of C. albicans differ in virulence for mice, only recently has it been shown that distinct isolates elicit antibodies that show substantially different patterns of epitope recognition and that differ in their ability to confer protection in vivo 10 . The present study has extended these observations to the cellular arm of the immune system, by showing that both neutrophils and macrophages from tissue‐susceptible and tissue‐resistant mice show quantitative differences in phagocytosis and killing of the three isolates of the yeast.…”

“…This result is consistent with the increased severity of tissue damage in CBA/CaH as compared with BALB/c mice. The differences in killing of the various yeast isolates, seen after opsonization with normal serum, may be correlated to various surface properties of the yeasts, such as the ability to bind complement regulatory proteins that can inhibit the binding of opsonins to the cell surface, 19 but as the three yeast isolates elicit distinct antibody profiles after systemic immunization, 10 differences in the killing efficiency after opsonization with immune serum are probably correlated to the specificity of antibodies raised against the individual yeasts. Our study was able only to measure the additive effect of antibody over and above the effect of complement in normal serum and hence the sensitivity of detection of specific antibody‐mediated effects may have been low.…”

“…Serum‐mediated enhancement of phagocytosis and killing of C. albicans by macrophages has been repeatedly shown in both human and animal systems and the present study showed that the effects of opsonization depended on the combination of mouse strain, yeast isolate and the type of serum used (normal or immune) 22 , 23 , 24 . The results probably reflect differences in the mode of interaction of opsonized yeasts with Fc receptors and receptors for components of the complement system, 25 as well as differences in the specificity and isotype of antibody produced after infection 10 . It is, however, recognized that properties of distinct yeast isolates, such as the presence of mannoprotein fibrils may also alter susceptibility to intracellular killing 26 …”

“…Bone marrow derived phagocytic cells are crucial for host defence against C. albicans infections and the increased production of neutrophils by bone marrow cells from BALB/c as compared with CBA/CaH mice in vitro is consistent with a fundamental role for the cellular arm of the innate immune system in the expression of genetically determined patterns of susceptibility and resistance. In addition, the variations shown in phagocytic responses may underlie observed differences in the severity of infections by the individual yeasts in vivo 10 …”

“…We have previously shown that three distinct isolates of C. albicans differ in their ability to establish both systemic and oral infections and in the specificity and protective effects of antibodies raised against them; 10 hence, the aims of this study were to compare phagocytosis and killing of these strains of C. albicans by neutrophils and macrophages from mice that showed mild (BALB/c) or severe (CBA/CaH) tissue damage 11 and to evaluate the effects of serum opsonins on these responses.…”