TBX21 participates in innate immune response by regulating Toll‐like receptor 2 expression in Streptococcus pneumoniae infections

Abstract

Nasopharyngeal carriage of Streptococcus pneumoniae (pneumococcus) plays an important role in the development of invasive diseases, and is also critically involved in setting up respiratory bacterial and viral infections. We previously reported that pneumococcus, one of the commonly carried bacteria in the nasopharynx, regulates non-typeable Haemophilus influenzae-induced inflammation by upregulating the expression of Toll-like receptor 2 (TLR2). However, the underlying molecular mechanisms by which TLR2 expression is regulated during pneumococcal infections have not yet been well characterized. TBX21 is an important transcription factor of adaptive immunity, but there is an increasing body of evidence pointing to a role in regulating innate immunity. The expression of TBX21 was reported in epithelial cells, but the expression and role of TBX21 in respiratory epithelium, especially for regulating TLR2, has not yet been studied. In this study, we found that pneumococcus upregulates TBX21 expression in the respiratory epithelium. The effect of pneumococcus on TBX21 expression was dependent on its cytoplasmic toxin, pneumolysin. In addition, epithelial TBX21 expression was not regulated by the gram-negative bacterium non-typeable Haemophilus influenzae, peptidoglycan or endotoxin. Deficiency of TBX21 in mice or knocking down TBX21 in epithelial cells suppressed pneumococcus-induced TLR2 expression, but not that of TLR4 or TLR9. These results indicate that the adaptive immune regulator TBX21 participates in regulating innate immune responses, through regulation of TLR2 expression during pneumococcal infections.

Panel 3: Genetics and Precision Medicine of Otitis Media

“…The mouse model is a useful tool to study and identify the genes relevant to OM. The advance in genetic studies through mutant mice is summarized in Table 1 30‐61 …”

“…Tbx21-deficient mice (C.129S-Tbx21tm1Glm/J) TBX21 regulating innate immune responses, via TLR2 during pneumococcal infections. 33…”

Combined Analysis of RRBS DNA Methylome and Transcriptome Reveal Novel Candidate Genes Related to Porcine Clostridium perfringens Type C-Induced Diarrhea

“…TBX21 is an important transcription factor of adaptive immunity that regulates the Th1/Th2 balance and increasing evidence has pointed to the critical roles in regulating innate immunity, cytokine balance, immune dysregulation, and bacterial infection. A study reported that pneumococcus upregulated TBX21 expression in the respiratory epithelium, knocking down TBX21 suppressed pneumococcus-induced TLR2 expression (Woo et al, 2014), and a change of TBX21 may lead to the dysregulation of type I interferon pathways and T cell pathways (Gourh et al, 2009). These studies have proved the adaptive immune regulator TBX21 participated in regulating host innate immune responses during pathogenic bacterial infections.…”

Innate Immunity in the Middle Ear Mucosa

“…Recent profiling of the cells within the murine middle ear using single-cell transcriptomics identified 17 different cell clusters, reflecting different cell types within the normal middle ear however tissue monocytes appear to have a primary role in regulation of acute middle ear infection response in the complex innate defence (Ryan et al, 2020). Interestingly, adaptive immune system factors such as TBX21, a transcription factor, may also participate in innate immune response regulation during S. pneumoniae infection, through modifying TLR2 expression (Woo C. H. et al, 2014). Whilst these model studies establish a link between innate and adaptive immune responses in the middle ear, additional studies are needed to confirm such links in the human middle ear.…”