Exhausted KLRG1hi CD8+ T and pathogenic GZMA+ Th17 cells are associated with the mild Mycoplasma pneumoniae pneumonia in children.

Mycoplasma pneumoniae (MP) infection in children has recently re-emerged with a higher rate of hospitalization in the post-COVID-19 period. However, understanding of how the adaptive immunity plays a role in the bacterial pneumonia is often restrained by recurrent infection and complex co-infection with M. pneumoniae. Herein, we took advantage of the single-cell RNA sequencing (scRNA-seq) and high-dimensional flow cytometry to characterize the impairment of peripheral T and B lymphocytes in pediatric patients with mild Mycoplasma pneumonia (MMPP). These patients were M. pneumoniae mono-infected at hospitalization, and showed an expansion of both effector and memory CD8+ T cells, with exhausted KLRG1hi CD8+ T compartments prevailed. Moreover, they exhibited a hyperactivation of IgM+ plasma cells and unswitched memory B cells, which could partly explain the IgM seroconversion routinely diagnosed in MMPP. Therefore, the hypo-functional CD8+ T cells and polarization of IgM secreting cells might help explain the ill-controlled bacterial replication in MMPP. Furthermore, compared to the healthy controls, IL-17A producing Th17 cells were reduced in MMPP, but cytotoxic granzymes increased significantly. Reduced IL-17A would suggest elevated M. pneumoniae colonization and reduced bacterial clearance in the respiratory tract, whereas cytotoxic property of this pathogenic Th17 cells might play a role in the pulmonary hyper inflammation. Therefore, this work managed to characterize the landscape of dysfunctional T and B lymphocytes that associates with the immune evasion and immunopathogenesis of MMPP.