Eradicating HIV Binding Site on Leukocytes Blocks Effects of Lethal Staphylococcus Toxin

aureus-mediated killing of host cells. Although many years have passed since the first description of staphylococcal leukocidal activity, the host factors responsible for the selectivity of leukotoxins towards different immune cells remain unknown.

In this regard, a recent paper revealed results of collaboration between bacteriologists and virologists at the New York University School of Medicine (NY, USA). These investigators focused their attention on C-C chemokine receptor type 5 (CCR5), a protein chemokine receptor on the surface of white blood cells by which T cells are attracted to specific tissue and organ targets. Many forms of HIV, the virus that causes AIDS, initially use CCR5 to enter and infect host cells. A few individuals carry a mutation known as CCR5-delta32 in the CCR5 gene, protecting them against these strains of HIV.

The investigators reported in the December 12, 2012, online edition of the journal Nature that they had identified CCR5 as a cellular determinant required for cytotoxic targeting of subsets of myeloid cells and T lymphocytes by the S. aureus leukotoxin ED (LukED). They showed that in experiments on cells growing in culture that LukED-dependent cell killing was blocked by CCR5 receptor antagonists, including the HIV drug maraviroc.

In a series of animal experiments, it was found that mice that had been genetically engineered to lack the gene for CCR5 were largely resistant to lethal S. aureus infection, which highlighted the importance of CCR5 targeting in S. aureus pathogenesis.

"What are the chances that a drug for HIV could possibly treat a virulent Staph infection?" asked senior author Dr. Victor J. Torres, assistant professor of microbiology at the New York University School of Medicine. "These findings are the result of a fantastic collaboration that we hope will result in significant clinical benefit. The goal in blocking the toxin with maraviroc or similar agents is to give the upper hand to the immune system to better control the infection."

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