CFP-10 from Mycobacterium tuberculosis selectively activates human neutrophils through a pertussis toxin-sensitive chemotactic receptor.

Abstract

Upon infection with Mycobacterium tuberculosis, neutrophils are massively recruited to the lungs, but the role of these cells in combating the infection is poorly understood. Through a type VII secretion system, M. tuberculosis releases a heterodimeric protein complex, containing a 6-kDa early secreted antigenic target (ESAT-6) and a 10-kDa culture filtrate protein (CFP-10), that is essential for virulence. Whereas the ESAT-6 component possesses multiple virulence-related activities, no direct biological activity of CFP-10 has been shown, and CFP-10 has been described as a chaperone protein for ESAT-6. We here show that the ESAT-6:CFP-10 complex induces a transient release of Ca(2+) from intracellular stores in human neutrophils. Surprisingly, CFP-10 rather than ESAT-6 was responsible for triggering the Ca(2+) response, in a pertussis toxin-sensitive manner, suggesting the involvement of a G-protein-coupled receptor. In line with this, the response was accompanied by neutrophil chemotaxis and activation of the superoxide-producing NADPH-oxidase. Neutrophils were unique among leukocytes in responding to CFP-10, as monocytes and lymphocytes failed to produce a Ca(2+) signal upon stimulation with the M. tuberculosis protein. Hence, CFP-10 may contribute specifically to neutrophil recruitment and activation during M. tuberculosis infection, representing a novel biological role for CFP-10 in the ESAT-6:CFP-10 complex, beyond the previously described chaperone function.

• Authors: Amanda Welin, Halla Björnsdottir, Malene Winther, Karin Christenson, Tudor Oprea, Anna Karlsson, Huamei Forsman, Claes Dahlgren, Johan Bylund
• Journal: Infection and immunity (Infect Immun) Vol. 83 Issue 1 Pg. 205-13 (Jan 2015) ISSN: 1098-5522 [Electronic] United States
• PMID: 25332123 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Antigens, Bacterial
• Bacterial Proteins
• CFP-10 protein, Mycobacterium tuberculosis
• ESAT-6 protein, Mycobacterium tuberculosis
• NADPH Oxidases
• Calcium

Topics

• Antigens, Bacterial (immunology)
• Bacterial Proteins (immunology)
• Calcium (metabolism)
• Cells, Cultured
• Chemotaxis
• Humans
• Mycobacterium tuberculosis (immunology)
• NADPH Oxidases (metabolism)
• Neutrophils (immunology, physiology)