Xinru Li,1,* Qianrui Zeng,1,* Chang Liu,1 Xinchao Yi,2 Haodang Luo,2 Qin Tong,3 Hongliang Chen,4 Xiaoxing You1 

1Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, People’s Republic of China; 2Department of Clinical Laboratory, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang, 421001, People’s Republic of China; 4Chenzhou No. 1 People’s Hospital (The Affiliated Chenzhou Hospital), Hengyang Medical College, University of South China, Chenzhou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Hongliang Chen, Chenzhou No. 1 People’s Hospital (The Affiliated Chenzhou Hospital), Hengyang Medical College, University of South China, Chenzhou, People’s Republic of China, Tel/Fax +86-735-2343595, Email chenhongliang2007@126.com Xiaoxing You, Institute of Pathogenic Biology, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang Medical College, University of South China, Hengyang, People’s Republic of China, Tel/Fax +86-734-8283366, Email youxiaoxing@usc.edu.cn

Abstract: Mycoplasma pneumoniae is a prevalent respiratory microbe that causes acute inflammation in the respiratory system. Surfactant proteins (SP), particularly SP-A and SP-D, are essential for the immunological protection against M. pneumoniae infection. Variant SP-A2 may lead to immune reactions, which could account for the variability in clinical manifestations among individuals. Mechanistically, these surfactant proteins may act as candidate receptors, facilitating both the adhesion of M. pneumoniae and internalization of community-acquired respiratory distress syndrome toxin. They also exhibit a high affinity for lipid ligands on the surface of M. pneumoniae membranes via their carbohydrate recognition domains, which aid in the direct clearing of the bacteria. In addition, SP-A and SP-D demonstrated synergistic effects in augmenting the intake and elimination of M. pneumoniae by alveolar macrophages. Furthermore, these surfactant proteins negatively regulate pulmonary inflammation by influencing lymphocyte and dendritic cell activities, reducing airway eosinophilic infiltration, and managing asthma-related inflammatory responses. A thorough understanding of the immunomodulatory roles of surfactant proteins in M. pneumoniae infection will shed light on how homeostasis is preserved during mycoplasma pneumonia and may guide the development of novel therapeutic strategies against this organism.

Keywords: Mycoplasma pneumoniae, surfactant protein-A, surfactant protein-D, immune modulation