34 kDa MOMP of Shigella flexneri promotes TLR2 mediated macrophage activation with the engagement of NF-kappaB and p38 MAP kinase signaling
Authors: Nibedita Mahata
Debasis Pore
Manoj K Chakrabarti
Amit Pal
Journal: Molecular Immunology (2010)
Discipline: IMMUNOLOGY
Keywords: MOMP; TLR2; macrophages; cytokines; chemokines
Affiliations: Division of Pathophysiology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road, Scheme-XM, Beliaghata, Kolkata 700010, West Bengal, India.

Abstract:  The 34 kDa major outer membrane protein (MOMP) of Shigella flexneri 2a induces combinatorial expression of TLR2 and TLR6 on peritoneal macrophages of BALB/c mice. Between the two best-characterized TLRs, to date, TLR2 and TLR4, which are chiefly responsible for recognizing majority of bacterial products, TLR2 alone participates in recognition of 34 kDa MOMP. In addition to TLRs, MOMP enhances the mRNA expression of MyD88 and TRAF6 and induces the nuclear translocation of NF-kappaB as well as activates p38 MAP kinase, suggesting the involvement of these molecules in the mechanism of action of MOMP. 34 kDa MOMP also stimulates macrophages, up regulates the surface expression of MHC-II and B7-1 and enhances the production of different cytokines (such as ILp70, TNF-alpha, Il-6) and chemokines (like MIP-1 alpha, MIP-1 beta and RANTES). The ability of the protein in the activation of macrophages, i.e. the induction of nuclear translocation of NF-kappaB and secretion of cytokines are dependent on TLR2 expression as demonstrated by the lack of response by macrophages pre-treated with inhibitory TLR2 mAb. Moreover, it has been found that MOMP induced regulation of TLR2 gene expression is dependent on NF-kappaB and p38 MAP kinase in murine macrophages for the first time. The MOMP induced cytokines and chemokines profile reflect that the protein has the ability to translate innate towards type-1 adaptive response. In conclusion MOMP recognizes by and activates macrophages which may be an initiating event in the antibacterial host response. 

Retracted: No

PubPeer comments:
 ![file] Concern with Figure 2C GAPDH bands look very similar. , 
 ![file] Image duplication , 
 Figure 4B: I am deeply disturbed to see your comment that the GAPDH bands look very similar. However, after receiving your comment we examined the Figure 4B closely and did a densitometric analysis of GAPDH bands and the values are embedded in the figure. You may see that the densitometric values are different for the individual band, indicating that each band has separate entity. ![file] Figure 6B: I am deeply disturbed to see your comments as we did not do any image duplication. However, after receiving your comments we examined the Figure 6B closely and did a densitometric analysis of GAPDH bands and the values are embedded in the figure. You may see that the densitometric values are different for the individual band, which you have stated to be duplicated, indicating that each band has separate entity. Figure 6C: I am deeply disturbed to see your comments as we did not do any image duplication. However, after receiving your comments we examined the Figure 6C closely and did a densitometric analysis of beta-actin bands and the values are embedded in the figure. You may see that the densitometric values are different for the individual band, which you have stated to be duplicated, indicating that each band has separate entity. ![file] ,