Streptococcus pneumoniae (Spn) is the most common etiology of bacterial pneumonia, which is one of the leading causes of death in children and the elderly worldwide. During non-lethal infections with Spn, immune cells accumulate in the lungs and protect against reinfection with more lethal strains, this protection is termed heterotypic immunity. Lymphocyte populations such as resident memory T cells and resident memory B cells are known to be crucial for heterotypic immunity, but their diversity remains understudied. Here, we aimed to elucidate resident lymphocyte heterogeneity in the lungs after recovery from pneumococcal pneumonia, and their contributions to heterotypic immune protection.
We developed a comprehensive immunophenotyping panel for full-spectrum flow cytometry (FSFC) to identify novel subsets of lymphocytes and combined it with an unbiased analysis approach. With this tool we discovered that murine lungs were enriched for unexpected subsets of resident lymphocytes, and we defined CD73 as a potential lymphocyte residence marker. We discovered a novel subset of CD4+ T cells defined by the phenotype CD11a+CD69+GL7+, which corresponded to a significant proportion of lung CD4+ TRM cells. Initial analyses demonstrated GL7+ T cells resembled CD4+ TRM cells. Functional studies revealed that unlike GL7- TRM subsets that were mostly RORT+, GL7+ TRM cells were also Gata-3+ and/or T-bet+ could secrete type 2 or type 1 cytokines, suggesting they were poised to be TH2 or TH1-like in function.
This study emphasizes the use of a multiparameter panel for FSFC as tool to identify novel lymphocyte subsets. We conclude that the environment of pneumonia-recovered lungs contains heterogeneous subsets of resident lymphocytes, including GL7+ TRM cells. We propose these subsets may contribute to lung immunity in unique ways and may be important players in serotype-independent protection to pneumococcal pneumonia. / 2024-01-23T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/45509 |
| Date | 24 January 2023 |
| Creators | Lyon De Ana, Carolina |
| Contributors | Mizgerd, Joseph P. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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