Laminin receptor initiates bacterial contact with the blood brain barrier in experimental menningitis models

Carlos J. Orihuela et al., J. Clin. Invest. 2009; 119:1638-1646

Speaker: Chih-Yu Huang (黃智郁)                       Time: 14:10-15:00, March 17, 2010

Commentator: Dr. Jiunn-Jong Wu (吳俊忠) Place: Room 601

Abstract:

Many infectious agents, e.g., certain neurotropic viruses and bacteria, can infect the human and cause devastating meningitis. Bacterial meningitis is the most serious infectious disease of early childhood, especially that caused by one of the three respiratory bacteria, Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. Previous studies have indicated that S. pneumoniae may be internalized by blood brain barrier (BBB) cells via interaction with the platelet activating factor receptor ¹, but the mechanism that mediates bacteria contact with the BBB cells is still unknown. It has been shown that the neurotropic viruses such as sindbis and adeno-associated viruses can bind to the laminin receptor (LR), and then invade into the central nervous system^2,3. The authors presumed that the bacteria might interact with the BBB cells via similar receptor. In this study, they demonstrated that indeed S. pneumoniae, H. influenzae, and N. meningitidis could bind to the 37/67-kDa LR and then initiate the bacterial contact with BBB. However, the binding domain in LR recognized by these bacterial pathogens, which was situated in the carboxyl terminus, was different from those recognized by neurotropic virus and laminin. The identified bacterial LR-binding adhesins were pneumococcal CbpA, meningococcal PilQ and PorA, and Omp2 of H. influenzae. They also found that CbpA_P392-R393 was the main interaction site with LR. Collectively, these results suggest that LR can mediate meningitis caused by a variety of infectious agents and it could be a novel therapeutic target for these pathogens.

References:

1.        Axel Ring et al., Pneumococcal trafficking across the blood-brain barrier: molecular analysis of a novel bidirection pathway. J. Clin. Invest.  1998;102:347-360

2.        Wang, K., et al., High affinity laminin receptor is a receptor for Sindbis virus in mammalian cells. J. Virol. 1992;66:4992-5001

3.        Akache, B., et al., The 37/67 kilodalton laminin receptor is a receptor for adeno-associated virus serotypes 8, 2, 3 and 9. J. Virol. 2006;80:9831-9836