Killing of Cryptococcus neoformans strains by human neutrophils and monocytes

Abstract

The susceptibility of various strains of Cryptococcus neoformans to killing by human polymorphonuclear leukocytes (PMNs) and monocytes was investigated. Five previously characterized strains of C. neoformans serotype A, a capsule-free mutant, and six recent clinical isolates were compared. PMNs and monocytes were isolated from normal peripheral blood and allowed to adhere to the flat-bottom wells of microtiter plates. Yeast cells of C. neoformans were added in the presence of normal human serum, and the plates were incubated at 37 degrees C. After 4 h, killing was determined by comparing the quantitative plate counts of viable yeast cells in experimental wells with counts in control wells containing yeast cells in the absence of leukocytes. No appreciable growth of yeast cells occurred in the wells during the incubation period. Both PMNs and monocytes effectively killed yeast cells at effector-to-target ratios as low as 1:1, although monocytes failed to kill the capsule-free strain 602 at a 1:1 ratio. With 9 of 12 strains, PMNs killed C. neoformans more effectively than did monocytes. Significant interstrain variation in killing occurred for both monocytes and PMNs, and the recent, clinical isolates were more resistant to killing by monocytes and PMNs than were the previously characterized strains. The extent to which different strains were killed by monocytes and PMNs was not consistently related to the size of the capsule or the entire cell. Normal PMNs and monocytes are remarkably effective in killing strains of C. neoformans in the absence of specific antibody and appear to constitute a significant defense mechanism in the peripheral circulation.

Killing of Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus by human polymorphonuclear leukocytes in serum and saliva

“…However, the opposite was observed with A. actinomycetemeomitans, • indicating a strain-dependent variation in the ability of this species to resist phagocytic killing. Furthermore, the laboratory strains appeared in general more susceptible than the fresh isolates, as also observed with other microorganisms (27). In a previous study (29), no statistically significant differences were observed in the killing of the various strains.…”

How do microbes evade neutrophil killing?

“…This loss of TNFR desensitizes neutrophils to TNF-a and is another strategy employed by the fungus to avoid contact with phagocytes (Dong and Murphy, 1996;Coenjaerts et al, 2001). These findings demonstrate that while C. neoformans is susceptible to phagocytosis and killing of human neutrophils (Miller and Mitchell, 1991), it can evade neutrophils altogether by suppressing their migration.…”

Th1‐Th2 Cytokine Kinetics in the Bronchoalveolar Lavage Fluid of Mice Infected with Cryptococcus neoformans of Different Virulences

“…In the present study, we compared differences in the host response to the intra-tracheal inoculation of two strains of C. neoformans which had variable virulence in (I, 33). However, the presence of neutrophils did not lead to eradication of the microorganism although they are capable of killing C. neoformans through various intracellular as well as extracellular mechanisms (2,5,11,28). In this context, impaired neutrophil antifungal activity has been reported in mice with invasive aspergillosis in spite of neutrophilia associated with the predominant production of IL-4 by CD4+ splenocytes (3).…”