IL-8 Increases Transmission of HIV Type 1 in Cervical Explant Tissue

Abstract

Interleukin-8 (IL-8) is the predominant cytokine expressed in the female genital tract of women with certain infectious/inflammatory conditions. IL-8 increased HIV-1 replication in T cells and to a greater extent in monocytes/macrophages in vitro. Physiological levels of IL-8 increased susceptibility to HIV-1 infection 5- to 8-fold in cervical explant tissues. Competitive inhibition of the IL-8 receptor CXCR2 with the small molecule inhibitor SB225002 resulted in a 45-70% decrease in cervical explant susceptibility to HIV-1 infection.

Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

“…In contrast, dexamethasone (GR) strongly inhibited IL-8 (ϳ29-fold) and completely shut down TNF-␣ production. These results are important given that TNF-␣ and IL-6 are potent activators of HIV-1 expression (45,68,123) and that IL-8 has been shown to increase HIV-1 replication in cervical tissue explants (112). To determine whether the decrease in proinflammatory cytokine secretion corresponded with a decreased ability to activate HIV-1 replication in infected cells, cell culture supernatants from NR-and/or PAM3CSK4-treated MDMs were cultured with latently infected HIV-1 cell lines.…”

M1 and M2a Polarization of Human Monocyte-Derived Macrophages Inhibits HIV-1 Replication by Distinct Mechanisms

“…This chemokine has been shown to enhance HIV-1 replication in activated PBMC (52). CXCL8, a chemokine that is also increased during HIV-1 infection (53) and that has been shown to enhance HIV-1 replication in vitro (54,55), was significantly up-regulated in M1-MDM. This chemokine was partially down-regulated in four of five independent M2a MDM compared with control cultures (Table III).…”

Role of Semen in Modulating the Female Genital Tract Microenvironment – Implications for HIV Transmission

“…16,84 We also demonstrated that semen strongly potentiates vaginal epithelial TLR activation induced by their ligands. 16 Considering that physiological levels of pro-inflammatory cytokines enhance susceptibility to HIV-1 infection fivefold to eightfold in cervical explant tissues, 85 this heightened inflammatory response could have important ramifications for viral transmission.…”