Abstract
Antimicrobial peptides act as important innate immune defense mediators against invading microbes such as Streptococcus pneumoniae. Among a number of antimicrobial peptides, β-defensin 2 (BD2) has strong antimicrobial activity against S. pneumoniae. However, little is known about the molecular signaling mechanisms leading to the BD2 expression. Here, we report that BD2 is strongly induced by S. pneumoniae in human airway cells including human middle-ear cells. Among diverse pneumococcal virulence factors, pneumolysin is required for inducing BD2 whose expression is under the control of p38 mitogen-activated protein kinase (MAPK). Pneumolysin also selectively regulates the expression of MAPK phosphatase 1 (MKP1), which inhibits the p38 signaling pathway, thereby leading to upregulation of BD2 to mount an effective defense against S. pneumoniae infection. These results provide novel insights into the molecular mechanisms underlying the coordinative regulation of BD2 expression via p38-MKP1 in the pathogenesis of airway infectious diseases.
Citations
Citations to this article as recorded by

- The Yin and Yang of Pneumolysin During Pneumococcal Infection
Joana M. Pereira, Shuying Xu, John M. Leong, Sandra Sousa
Frontiers in Immunology.2022;[Epub] CrossRef - Streptococcus pneumoniae and Its Virulence Factors H2O2 and Pneumolysin Are Potent Mediators of the Acute Chest Syndrome in Sickle Cell Disease
Joyce Gonzales, Trinad Chakraborty, Maritza Romero, Mobarak Abu Mraheil, Abdullah Kutlar, Betty Pace, Rudolf Lucas
Toxins.2021; 13(2): 157. CrossRef -
Toll-like receptor 2-mediated induction of avian
β
-defensin 9 by
Lactobacillus rhamnosus
and its cellular components in chicken intestinal epithelial cells
Yongjie Jia, Wei Si, Zhimin Hong, Mingren Qu, Nianhua Zhu, Siguo Liu, Guanhong Li
Food and Agricultural Immunology.2019; 30(1): 398. CrossRef - Effector triggered immunity
Rajmohan Rajamuthiah, Eleftherios Mylonakis
Virulence.2014; 5(7): 697. CrossRef - Paeoniflorin Upregulates β-Defensin-2 Expression in Human Bronchial Epithelial Cell Through the p38 MAPK, ERK, and NF-κB Signaling Pathways
Yuying Gan, Xuefan Cui, Ting Ma, Yanliang Liu, Amin Li, Mao Huang
Inflammation.2014; 37(5): 1468. CrossRef