Mycobacterium bovis bacillus Calmette-Guerin induces CCL5 secretion via the Toll-like receptor 2-NF-kappaB and -Jun N-terminal kinase signaling pathways

Patricia Méndez-Samperio, Artemisa Trejo, Aline Pérez
Clinical and Vaccine Immunology: CVI 2008, 15 (2): 277-83
In response to Mycobacterium bovis bacillus Calmette-Guérin (BCG), CC chemokines are secreted from host cells to attract components of the innate and adaptive immune systems to the site of infection. Toll-like receptor 2 (TLR2) has been shown to recognize M. bovis BCG and to initiate signaling pathways that result in enhanced secretion of CC chemokines. Despite the essential requirement of TLR2 in M. bovis BCG infection, the mechanisms by which it induces secretion of CC chemokines are not well defined. In this study, we report that stimulation of HEK293 cells expressing human TLR2 with M. bovis BCG resulted in increased CCL2 and CCL5 secretion, as determined by an enzyme-linked immunosorbent assay. M. bovis BCG infection resulted in the activation of c-Jun N-terminal kinase (JNK), and the inhibition of JNK activity had a significant effect on M. bovis BCG-dependent CCL5 secretion in TLR2-expressing cells but no effect on M. bovis BCG-dependent CCL2 secretion from infected HEK293 cells expressing human TLR2. The M. bovis BCG-induced CCL5 release was attenuated by sulfasalazine (a well-described inhibitor of NF-kappaB activity), BAY 11-7082 (an IkappaB phosphorylation inhibitor), and ALLN (a well-described inhibitor of NF-kappaB activation that prevents degradation of IkappaB and eventually results in a lack of translocated NF-kappaB in the nucleus). In addition, stimulation of TLR2-expressing cells with M. bovis BCG resulted in translocation of NF-kappaB subunits from the cytoplasmic to the nuclear fraction, and stimulation of cells with M. bovis BCG activated IkappaB kinase alphabeta. These findings indicate that M. bovis BCG induces CCL5 production through mechanisms that include a TLR2-dependent component that requires JNK and NF-kappaB activities.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"