Staphylococcus aureus leukotoxin ED targets the chemokine receptors CXCR1 and CXCR2 to kill leukocytes and promote infection.

Abstract

The Staphylococcus aureus leukotoxin ED (LukED) is a pore-forming toxin required for the lethality associated with bacteremia in murine models. LukED targets the chemokine receptor CCR5 to kill T lymphocytes, macrophages, and dendritic cells. LukED also kills CCR5-deficient cells, like neutrophils, suggesting the existence of additional cellular receptors. Here, we identify the chemokine receptors CXCR1 and CXCR2 as the targets of LukED on neutrophils. The LukE subunit binds neutrophils in a specific and saturable manner, and this interaction is inhibited by CXCL8, the high-affinity endogenous ligand of CXCR1 and CXCR2. LukED recognition of CXCR1 and CXCR2 promotes the killing of monocytes and neutrophils in vitro. LukED-mediated targeting of CXCR1 and CXCR2(+) cells contributes to S. aureus pathogenesis and facilitates lethality in systemically infected mice. Thus, LukED is a versatile toxin that endows S. aureus with the ability to simultaneously disarm both innate and adaptive compartments of the host immune response.

• Authors: Tamara Reyes-Robles, Francis Alonzo 3rd, Lina Kozhaya, D Borden Lacy, Derya Unutmaz, Victor J Torres
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 14 Issue 4 Pg. 453-9 (Oct 16 2013) ISSN: 1934-6069 [Electronic] United States
• PMID: 24139401 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Bacterial Proteins
• Exotoxins
• LukD protein, Staphylococcus aureus
• LukE protein, Staphylococcus aureus
• Receptors, Interleukin-8A
• Receptors, Interleukin-8B

Topics

• Animals
• Bacterial Proteins (metabolism)
• Cell Survival (drug effects)
• Disease Models, Animal
• Exotoxins (metabolism)
• Host-Pathogen Interactions
• Humans
• Mice
• Monocytes (drug effects)
• Neutrophils (drug effects)
• Receptors, Interleukin-8A (metabolism)
• Receptors, Interleukin-8B (metabolism)
• Staphylococcal Infections (pathology)
• Staphylococcus aureus (metabolism, pathogenicity)
• Survival Analysis
• Virulence