Acute neutropenia decreases inflammation associated with murine vaginal candidiasis but has no effect on the course of infection

Abstract

We have used a mouse model of vaginal candidiasis to determine the effect of neutrophil depletion on (a) the clearance of Candida albicans and (b) the degree of inflammation associated with infection. No differences in recoverable yeast number or rate of clearance were observed between normal and neutrophil-depleted mice; however, vaginal inflammation was significantly decreased in neutrophil-depleted animals.

FIG. 1

Neutrophil depletion does not affect infection. Vaginal washes at day 5 postinfection were plated, and the numbers of recoverable yeast cells (CFU) were counted. Neither recoverable yeast numbers nor clearance rates (shown as percentages) were significantly different between control and neutrophil-depleted mice. CFU for individual mice are shown (n = 12). These data are representative of two separate experiments. Horizontal bars indicate average values.

FIG. 2

Vaginal histology of C. albicans-infected mice. (A) PAS stain of a vaginal section from a control mouse shows a florid infection with pseudohyphae (PH) and blastoconidia (B) penetrating the cornified epithelium. The lumen (L), mucosa (M), and submucosa (SM) are denoted for orientation. Magnification, ×83. (B) H&E stain of a vaginal section from the same mouse as in panel A. Neutrophils are present in the mucosa and have formed a microabscess (MA) in the cornified epithelium. Significant edema and submucosal fibroblastic disorganization are also present. Magnification, ×83. (C) PAS stain of a vaginal section from a neutrophil-depleted mouse. Pseudohyphae (PH) are present in the cornified epithelium in numbers similar to those of control mice. No blastoconidia are seen, and the pseudohyphae form short stubby chains. Magnification, ×83. (D) H&E stain of a vaginal section from a neutrophil-depleted mouse shows a profound lack of neutrophils in either the cornified epithelium or mucosa. Some edema has occurred, but the severity of inflammation is significantly less than that in the control animals. Magnification, ×83. (E) H&E stain of a vaginal section from a noninfected mouse 3 days after estrogen administration. No microabscesses are evident, and PMN infiltration is minimal. Magnification, ×83.

FIG. 2

Vaginal histology of C. albicans-infected mice. (A) PAS stain of a vaginal section from a control mouse shows a florid infection with pseudohyphae (PH) and blastoconidia (B) penetrating the cornified epithelium. The lumen (L), mucosa (M), and submucosa (SM) are denoted for orientation. Magnification, ×83. (B) H&E stain of a vaginal section from the same mouse as in panel A. Neutrophils are present in the mucosa and have formed a microabscess (MA) in the cornified epithelium. Significant edema and submucosal fibroblastic disorganization are also present. Magnification, ×83. (C) PAS stain of a vaginal section from a neutrophil-depleted mouse. Pseudohyphae (PH) are present in the cornified epithelium in numbers similar to those of control mice. No blastoconidia are seen, and the pseudohyphae form short stubby chains. Magnification, ×83. (D) H&E stain of a vaginal section from a neutrophil-depleted mouse shows a profound lack of neutrophils in either the cornified epithelium or mucosa. Some edema has occurred, but the severity of inflammation is significantly less than that in the control animals. Magnification, ×83. (E) H&E stain of a vaginal section from a noninfected mouse 3 days after estrogen administration. No microabscesses are evident, and PMN infiltration is minimal. Magnification, ×83.

FIG. 3

Neutrophil depletion decreases vaginal inflammation. Histologic sections were graded as described in the text. No statistical difference in floridity between control and neutrophil-depleted mice was observed; however, both the level of PMN infiltration (P < 0.001) and the degree of inflammation (P < 0.05) were significantly decreased in the neutrophil-depleted mice. The average scores ± standard errors (indicated by error bars) are graphed (n = 2). Results are representative of two separate experiments. Open bars, neutrophil-depleted mice; shaded bars, control mice. Asterisks indicate significant differences.