Mycoplasma pneumoniae Compared to Streptococcus pneumoniae Avoids Induction of Proinflammatory Epithelial Cell Responses despite Robustly Inducing TLR2 Signaling

Mycoplasma pneumoniae and Streptococcus pneumoniae are the most common bacterial causes of pneumonia in children. The clinical characteristics of pneumonia differ significantly between the two bacteria. We aimed to elucidate the differences in pathogenesis between M. pneumoniae and S. pneumoniae by...

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Published in:	Infection and immunity Vol. 90; no. 8; p. e0012922
Main Authors:	de Groot, R C A, Zhu, H, Hoogenboezem, T, de Bruijn, A C J M, Eenjes, E, 't Jong, A E J, Belo, A I, Estevão, S C, Bajramovic, J J, Rottier, R J, Kool, M, van Rossum, A M C, Unger, W W J
Format:	Journal Article
Language:	English
Published:	United States American Society for Microbiology 18-08-2022
Subjects:	Child Cytokines Epithelial Cells Host Response and Inflammation Host-Microbial Interactions Humans Interleukin-33 Interleukin-8 Mycoplasma pneumoniae Spotlight Selection Streptococcus pneumoniae Toll-Like Receptor 2 - genetics host response pneumonia respiratory pathogens Mycoplasma pneumoniae TLR10 IL-8 primary bronchial epithelial cells IL-33 Streptococcus pneumoniae TLR2
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Summary:	Mycoplasma pneumoniae and Streptococcus pneumoniae are the most common bacterial causes of pneumonia in children. The clinical characteristics of pneumonia differ significantly between the two bacteria. We aimed to elucidate the differences in pathogenesis between M. pneumoniae and S. pneumoniae by characterizing the respiratory epithelial cell immune response to both pathogens. Using primary human bronchial epithelial cells in air-liquid interface cultures, we observed lower production of the proinflammatory cytokines interleukin-6 (IL-6) and IL-8 in response to M. pneumoniae than to S. pneumoniae. In contrast to the differences in proinflammatory cytokine production, Toll-like receptor 2 (TLR2)-mediated signaling in response to M. pneumoniae was stronger than to S. pneumoniae. This difference largely depended on TLR1 and not TLR6. We found that M. pneumoniae, but not S. pneumoniae, also induced signaling of TLR10, a coreceptor of TLR2 that has inhibitory properties. M. pneumoniae-induced TLR10 signaling on airway epithelial cells was partially responsible for low IL-8 production, as blocking TLR10 by specific antibodies increased cytokine production. M. pneumoniae maintained Th2-associated cytokine production by epithelial cells, which concurs with the known association of M. pneumoniae infection with asthma. M. pneumoniae left IL-33 levels unchanged, whereas S. pneumoniae downregulated IL-33 production both under homeostatic and Th2-promoting conditions. By directly comparing M. pneumoniae and S. pneumoniae, we demonstrate that M. pneumoniae avoids induction of proinflammatory cytokine response despite its ability to induce robust TLR2 signaling. Our new findings suggest that this apparent paradox may be partially explained by M. pneumoniae-induced signaling of TLR2/TLR10.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors declare no conflict of interest.
ISSN:	0019-9567 1098-5522
DOI:	10.1128/iai.00129-22