PMID:25332123

Citation	Welin, A, Björnsdottir, H, Winther, M, Christenson, K, Oprea, T, Karlsson, A, Forsman, H, Dahlgren, C and Bylund, J (2015) CFP-10 from Mycobacterium tuberculosis selectively activates human neutrophils through a pertussis toxin-sensitive chemotactic receptor. Infect. Immun. 83:205-13
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.
Links	PubMed PMC4288871 Online version:10.1128/IAI.02493-14
Keywords	Antigens, Bacterial/immunology; Bacterial Proteins/immunology; Calcium/metabolism; Cells, Cultured; Chemotaxis; Humans; Mycobacterium tuberculosis/immunology; NADPH Oxidase/metabolism; Neutrophils/immunology; Neutrophils/physiology
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MYCTU:ESXB		GO:0030593: neutrophil chemotaxis	ECO:0000314:		P		Figure 3 (A)Cells migrated more with higher concentration CFP-10.	complete CACAO 11309
MYCTU:ESXB		GO:0033864: positive regulation of NAD(P)H oxidase activity	ECO:0000314:		P		Figure 3 (B)Addition of CFP-10 stimulated neutrophils to produce more O2.	complete CACAO 11310

References

See Help:References for how to manage references in GONUTS.