Mycobacterium tuberculosis interferes with the response to infection by inducing the host EphA2 receptor.
BACKGROUND
Mycobacterium tuberculosis is an unusual pathogen, persisting for years in infected persons despite an immune response. Erythropoietin-producing hepatoma (Eph) receptors are critical for tissue organization. One hallmark of tuberculosis is the presence of granulomas consisting of organized immune cells. The importance of granuloma structure makes it likely that Eph receptors play a role in immunity to tuberculosis.


METHODS
We infected mice with low doses of M. tuberculosis by the aerosol method and examined the effects on ephA gene expression, pathology, composition of lymphocytes in the lungs (by flow cytometry), migration of CD4+ and CD8+ T cells, and numbers of cytokine-expressing cells.


RESULTS
Mice infected with M. tuberculosis displayed higher expression of ephA1 and ephA2 as well as ephrinA1, which encodes the ligand for EphA1 and EphA2. Interestingly, ephA2-/- mice displayed greater pathology, greater accumulation of T cells and dendritic cells, and higher levels of proinflammatory cytokines than did normal C57BL/6 mice. Furthermore, T cells from ephA2-/- mice migrated more efficiently than did those from C57BL/6 mice.


CONCLUSIONS
These observations suggest that ephA-related genes may provide a mechanism that M. tuberculosis uses to circumvent the host response, given that accumulation of T cells appears to be due to the inhibition of immune cell migration by EphA2. Ultimately, the absence of ephA2 results in greater clearance of M. tuberculosis during the chronic phase of infection, suggesting that induction of ephA2 is important for the survival of M. tuberculosis during latency.
Department of Microbial and Molecular Pathogenesis, Texas A&M University System Health Science Center, College Station, TX, USA.
Manirath
M
Khounlotham
Selvakumar
S
Subbian
Roger
R
Smith
Suat L G
SL
Cirillo
Jeffrey D
JD
Cirillo
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006099:Granuloma / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D036104:Receptor, EphA2 / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology; D014397:Tuberculosis, Pulmonary / Q000378:metabolism*
D016207:Cytokines; D036104:Receptor, EphA2