Killing of Coccidioides immitis by human peripheral blood mononuclear cells.

The ability of human peripheral blood mononuclear cells (MNL) obtained from healthy donors to kill the fungus Coccidioides immitis was examined in vitro with an assay that uses a single fungal particle per well. MNL killed 25.0% +/- 3.5% of a coccidioidal arthroconidial target, compared with the 4.7% +/- 2.9% killed by polymorphonuclear leukocytes obtained from the same donors (P = 0.012). Arthroconidial killing by MNL was not dependent on donor delayed dermal hypersensitivity to spherulin. Killing of another fungal target, Candida glabrata, was not significantly different between MNL and polymorphonuclear leukocytes (P = 0.783). Depletion of monocytes from MNL with Sephadex G-10 resulted in a significant reduction in arthroconidial killing (21.4% +/- 13.6% versus 2.4% +/- 3.4%; P = 0.025), while enrichment of monocytes by Percoll density gradient centrifugation or plastic adherence resulted in significantly increased arthroconidial killing compared with that by MNL (P = 0.005 and 0.001, respectively). Killing of 96-h spherules by MNL was 7.3% +/- 3.1%, significantly less than the 21.4% +/- 2.8% killing of arthroconidia in the same experiments (P = 0.016). Incubation of MNL with human recombinant gamma interferon or tumor necrosis factor alpha did not result in increased MNL killing of coccidioidal arthroconidia under various conditions. These results suggest that MNL have an inherent ability to kill coccidioidal arthroconidia in vitro which is not dependent on prior host exposure to C. immitis. This activity appears to reside in peripheral blood monocytes.

In vitro assessment of cellular immunity in human coccidioidomycosis: relationship between dermal hypersensitivity, lymphocyte transformation, and lymphokine production by peripheral blood mononuclear cells from healthy adults.

Dermal hypersensitivity in coccidioidomycosis was compared with three simultaneous measures of in vitro cellular immunity using 35 healthy donors living in an area endemic for coccidioidomycosis. Twenty donors had greater than 5 mm induration to usual-strength spherulin and were considered skin test-positive. Mononuclear cells from these individuals were more responsive by lymphocyte transformation (12,541 +/- 3746 vs. -112 +/- 260 cpm, P = .007) and produced significantly more interleukin-2 (3481 +/- 1067 vs. -5 +/- 69 cpm, P less than .001) and interferon-gamma (1831 +/- 481 vs. 75 +/- 58 pg/ml, P less than .001) than cells from skin test-negative donors in response to a coccidioidal antigen. However, the correlation between the skin test size and the magnitude of the in vitro response among skin test-positive donors was poor (R2 = 0.08, P = .24). These results indicate that healthy individuals with dermal hypersensitivity to Coccidioides immitis can be distinguished from those without hypersensitivity by their cellular in vitro response to a coccidioidal antigen.

Deferoxamine increases the susceptibility of beta-thalassemic, iron-overloaded mice to infection with Listeria monocytogenes.

The effect of the iron chelator deferoxamine (DFO) on resistance to infection with Listeria monocytogenes in mice with a condition analogous to human beta-thalassemia was studied. Intraperitoneal injection of 10 mg DFO resulted in significantly increased mortality when given one, three and six days before infection with L. monocytogenes (for all three time points, p less than 0.02). There were no significant differences in hematocrit, plasma iron, or splenic iron content between the two groups of mice during these time periods. In addition, splenic counts of L. monocytogenes were not significantly higher in DFO-treated compared to saline-treated mice three days after infection. Moreover, background C57Bl/6J mice were not more susceptible to Listeria infection after receiving DFO than were saline-treated controls. In conclusion, acute administration of DFO increases the susceptibility of beta-thalassemic mice to L. monocytogenes. The effect is not seen in background mice and suggests that DFO increases susceptibility to Listeria infection only in animals with iron overload.