PRELP Enhances Host Innate Immunity against the Respiratory Tract PathogenMoraxella catarrhalis.
Respiratory tract infections are one of the leading causes of mortality worldwide urging better understanding of interactions between pathogens causing these infections and the host. Here we report that an extracellular matrix component proline/arginine-rich end leucine-rich repeat protein (PRELP) is a novel antibacterial component of innate immunity. We detected the presence of PRELP in human bronchoalveolar lavage fluid and showed that PRELP can be found in alveolar fluid, resident macrophages/monocytes, myofibroblasts, and the adventitia of blood vessels in lung tissue. PRELP specifically binds respiratory tract pathogensMoraxella catarrhalis,Haemophilus influenzae, andStreptococcus pneumoniae, but not other bacterial pathogens tested. We focused our study onM. catarrhalisand found that PRELP binds the majority of clinical isolates ofM. catarrhalis(n= 49) through interaction with the ubiquitous surface protein A2/A2H.M. catarrhalisusually resists complement-mediated serum killing by recruiting to its surface a complement inhibitor C4b-binding protein, which is also a ligand for PRELP. We found that PRELP competitively inhibits binding of C4b-binding protein to bacteria, which enhances membrane attack complex formation onM. catarrhalisand thus leads to increased serum sensitivity. Furthermore, PRELP enhances phagocytic killing of serum-opsonizedM. catarrhalisby human neutrophils in vitro. Moreover, PRELP reducesMoraxellaadherence to and invasion of human lung epithelial A549 cells. Taken together, PRELP enhances host innate immunity againstM. catarrhalisthrough increasing complement-mediated attack, improving phagocytic killing activity of neutrophils, and preventing bacterial adherence to lung epithelial cells.
Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden.
Guanghui
0000-0001-8831-7739
G
Liu
Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden.
David
0000-0003-4600-9070
D
Ermert
Division of Pathology, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden; and.
Martin E
0000-0001-8510-3102
ME
Johansson
Division of Clinical Microbiology, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden.
Birendra
0000-0002-7246-1442
B
Singh
Division of Clinical Microbiology, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden.
Yu-Ching
0000-0003-3398-6294
YC
Su
Division of Clinical Microbiology, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden.
Magnus
0000-0003-1104-2727
M
Paulsson
Division of Clinical Microbiology, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden.
Kristian
0000-0001-6274-6965
K
Riesbeck
Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden; Anna.Blom@med.lu.se.
Anna M
0000-0002-1348-1734
AM
Blom
D000920:Antibody-Dependent Cell Cytotoxicity; D001422:Bacterial Adhesion; D002460:Cell Line; D051056:Complement Inactivating Agents / Q000037:antagonists & inhibitors / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology*; D001936:Moraxella catarrhalis / Q000276:immunology*; D045828:Moraxellaceae Infections / Q000276:immunology*; D058628:Myofibroblasts / Q000276:immunology*; D010587:Phagocytosis; D020545:Respiratory Mucosa / Q000276:immunology* / Q000473:pathology; D012141:Respiratory Tract Infections / Q000276:immunology*
D051056:Complement Inactivating Agents; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C096382:PRELP protein, human