Expression of toll-like receptors in genital tract tissues from normal and HIV-infected men

Abstract

Problem: cells of the innate immune system use Toll-like receptors (TLRs) to recognize and respond to invading pathogens. This study was carried out to characterize TLR expression in the human male genital tract, an initial infection site for several sexually transmitted pathogens.

Method of study: immunohistochemistry was used to detect expression of TLRs 1-9 in genital tract tissues from HIV(-) and HIV(+) men.

Results: in HIV(-) men, TLR1(+) leukocytes were detected throughout the genital tract. Leukocytes in the penile urethra also expressed TLRs2, 3, 5, 7 and 9. Epithelial cells in most tissues did not express TLRs; exceptions were the prostate, where TLRs3 and 8 were observed on the apical surface of luminal epithelial cells, and the penile urethra, where epithelial cells expressed TLR9. In genital tissues from HIV(+) men with AIDS, few TLR(+) cells were detected.

Conclusion: cells in the male genital tract can express a variety of TLRs. The penile urethra contained the highest number of TLR(+) cells, indicating that this tissue plays a major role in the innate immune defense of the male genital tract. Overall, TLR expression was reduced in genital tissues from HIV(+) men.

Fig. 1

Immunohistochemistry performed on a lymph node from an HIV⁺ man showing expression of (a) TLR2, (b) TLR3, (c) TLR4, (d) TLR5, (e) TLR7 and (f) CD68 (macrophage marker) all at × 150.

Fig. 2

TLR1 expression by cells in (a) interstitium of testis × 100, (b) stroma of efferent ducts × 175 and (c) epithelium of seminal vesicle × 150.

Fig. 3

TLR expression in prostate: (a) TLR3⁺ epithelium of glands × 180, (b) TLR3 expression limited to apical membrane of epithelial cells × 250, (c) TLR8⁺ granules in cytoplasm of epithelial cells × 200, d) TLR1⁺ cells in epithelium × 160 and (e) TLR7⁺ intraepithelial cell × 250.

Fig. 4

TLR expression in the urethral mucosa: (a) TLR9⁺ granules in cytoplasm of epithelial cells (arrows) and intensely stained TLR9⁺ intraepithelial cells × 200, (b) TLR1⁺ cells that resemble granulocytes in epithelium of fossa navicularis × 260, (c) TLR1⁺ cells that resemble macrophages in epithelium and lamina propria × 150, (d) TLR2⁺ cells in stroma and epithelium at tip of penis × 160, (e) TLR3⁺ cells in stroma and epithelium at tip of penis × 150 and (f) TLR5⁺ cells in epithelium and lamina propria of the urethra × 120.

Fig. 5

TLR expression by urethral mucosa: (a). TLR7⁺ intraepithelial cell × 260, (b) numerous TLR9⁺ cells located in the epithelium and lamina propria × 150 and (c) TLR9⁺ cells detected in the stroma of the corpus spongiosum × 160.

Fig. 6

TLR expression by genital tract tissue from HIV⁺ men: (a) TLR2⁺ cells in interstitium of testes × 180, (b) TLR7⁺ epithelial cells of epididymis × 175, (c) TLR8⁺ epithelial cells of epididymis × 175, (d) TLR9⁺ epithelial cells of epididymis × 175 and (e) TLR7⁺ intraepithelial cell in prostate gland × 250.