Moraxella catarrhalis is internalized in respiratory epithelial cells by a trigger-like mechanism and initiates a TLR2- and partly NOD1-dependent inflammatory immune response.
Moraxella catarrhalis is an important pathogen in patients with chronic obstructive lung disease (COPD). While M. catarrhalis has been categorized as an extracellular bacterium so far, the potential to invade human respiratory epithelium has not yet been explored. Our results obtained by electron and confocal microscopy demonstrated a considerable potential of M. catarrhalis to invade bronchial epithelial (BEAS-2B) cells, type II pneumocytes (A549) and primary small airway epithelial cells (SAEC). Moraxella invasion was dependent on cellular microfilament as well as on bacterial viability, and characterized by macropinocytosis leading to the formation of lamellipodia and engulfment of the invading organism into macropinosomes, thus indicating a trigger-like uptake mechanism. In addition, the cells examined expressed TLR2 as well as NOD1, a recently found cytosolic protein implicated in the intracellular recognition of bacterial cell wall components. Importantly, inhibition of TLR2 or NOD1 expression by RNAi significantly reduced the M. catarrhalis-induced IL-8 secretion. The role of TLR2 and NOD1 was further confirmed by overexpression assays in HEK293 cells. Overall, M. catarrhalis may employ lung epithelial cell invasion to colonize and to infect the respiratory tract, nonetheless, the bacteria are recognized by cell surface TLR2 and the intracellular surveillance molecule NOD1.
Slevogt
Hortense
H
Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité- Universitätsmedizin Berlin, 13353 Berlin, Germany. hortense.slevogt@charite.de
Seybold
Joachim
J
Tiwari
Krishna N
KN
Hocke
Andreas C
AC
Jonatat
Carola
C
Dietel
Solveig
S
Hippenstiel
Stefan
S
Singer
Bernhard B
BB
Bachmann
Sebastian
S
Suttorp
Norbert
N
Opitz
Bastian
B
D002460:Cell Line; D045744:Cell Line, Tumor; D004705:Endocytosis / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology / Q000648:ultrastructure; D005434:Flow Cytometry; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D045022:Lactate Dehydrogenases / Q000378:metabolism; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D001936:Moraxella catarrhalis / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*
D016209:Interleukin-8; D016328:NF-kappa B; D053474:Nod1 Signaling Adaptor Protein; D051195:Toll-Like Receptor 2; D045022:Lactate Dehydrogenases