CEACAM1 inhibits Toll-like receptor 2-triggered antibacterial responses of human pulmonary epithelial cells.

Scott Gray-Owen

Scott Gray-Owen

Scott Gray-Owen

+ -1 Evaluators

Can bacteria avoid detection by molecular pattern sensors of the innate immune system? In the case of human-restricted bacteria Moraxella catarrhalis and Neisseria meningitidis, it appears that they can. These two bacteria commonly reside within the nasopharynx of healthy individuals, yet also possess the capacity to cause disease when they spread from this site. This study reports that their specific attachment to the human cellular adhesion molecule CEACAM1 triggers a phosphatase-dependent inhibitory cascade that effectively suppresses toll-like receptor (TLR)-dependent signals that otherwise prompt the epithelial cell to recruit immune cells to the site of infection. This may help to explain why their simple presence in the nasopharynx does not elicit an inflammatory response.

Philipp M Lepper

Philipp M Lepper

Philipp M Lepper

Kathy Triantafilou

Kathy Triantafilou

Kathy Triantafilou

+ 0 Evaluators

The human body is a good place to live for many different micro-organisms and most of them don't cause relevant problems. Some pathogens can even colonize otherwise sterile places such as the gastric lumen (Helicobacter pylori) or the lumen of the lower respiratory tract (Moraxella catarrhalis). This study suggests that immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing receptors control TLR2-mediated inflammatory signals. There is an intensive interplay between host and microbe on the molecular level and many micro-organisms try to fly under the radar of the host's immunological surveillance or try to interact with the host in the way that the immune response is suppressed or even abrogated. Patients with chronic obstructive lung disease (COPD) are frequently colonized with M. catarrhalis and the pathogen causes approximately 25% of exacerbations of the disease. To modify the host immune response, some microbes have evolved different (and, interestingly, structurally unrelated) proteins, that _target the carcino-embryonic antigen-related cell adhesion molecules (CEACAMs). One of these proteins is the ubiquitous surface protein A1 (UspA1) of M. catarrhalis. Slevogt and colleagues report that interaction of M. catarrhalis with the protein CEACAM1, which is widely expressed on respiratory epithelia, initiates signals that suppress TLR2-induced Akt activation and inflammation. CEACAM1 contains an ITIM, which recruits the Src homology 2 domain-containing cytoplasmic protein tyrosine phosphatase 1 (SHP-1) upon phosphorylation. This initiates a negative loop by limiting phosphorylation of PI(3)K. The authors show that the TLR2-mediated release of IL-8 is significantly lower if UspA1 interacts with CEACAM1 and that CEACAM1 with its ITIM motif is critical for the inhibition of TLR2-driven NFkB activation. The study suggests that ITIM-bearing receptors control TLR2-mediated inflammatory signals. Possibly, this control is not only restricted to TLR2 but works for other TLRs as well. This could have implications in a wide variety of inflammatory/immunological disorders, including transplantation, where therapeutical intervention aims at suppression of inflammation. Novel drugs could _target CEACAMs to suppress inflammation. It is fascinating to see how microbes interact with our immune system to evade destruction.