Characterization of γδT cells in lung of Plasmodium yoelii-infected C57BL/6 mice

Abstract

Background Malaria has high morbidity and mortality rates in some parts of tropical and subtropical countries. Besides respiratory and metabolic function, lung plays a role in immune system. γδT cells have multiple functions in producing cytokines and chemokines, regulating the immune response by interacting with other cells. It remains unclear about the role of γδT cells in the lung of mice infected by malaria parasites. Methods Flow cytometry (FCM) was used to evaluate the frequency of γδT cells and the effects of γδT cells on the phenotype and function of B and T cells in Plasmodium yoelii-infected wild-type (WT) or γδTCR knockout (γδT KO) mice. Haematoxylin-eosin (HE) staining was used to observe the pathological changes in the lungs. Results The percentage and absolute number of γδT cells in the lung increased after Plasmodium infection (p < 0.01). More γδT cells were expressing CD80, CD11b, or PD-1 post-infection (p < 0.05), while less γδT cells were expressing CD34, CD62L, and CD127 post-infection (p < 0.05). The percentages of IL-4+, IL-5+, IL-6+, IL-21+, IL-1α+, and IL-17+ γδT cells were increased (p < 0.05), but the percentage of IFN-γ-expressing γδT cells decreased (p < 0.05) post-infection. The pathological changes in the lungs of the infected γδT KO mice were not obvious compared with the infected WT mice. The proportion of CD3+ cells and absolute numbers of CD3+ cells, CD3+ CD4+ cells, CD3+ CD8+ cells decreased in γδT KO infected mice (p < 0.05). γδT KO infected mice exhibited no significant difference in the surface molecular expression of T cells compared with the WT infected mice (p > 0.05). While, the percentage of IFN-γ-expressing CD3+ and CD3+ CD8+ cells increased in γδT KO infected mice (p < 0.05). There was no significant difference in the absolute numbers of the total, CD69+, ICOS+, and CD80+ B cells between the WT infected and γδT KO infected mice (p > 0.05). Conclusions The content, phenotype, and function of γδT cells in the lung of C57BL/6 mice were changed after Plasmodium infection. γδT cells contribute to T cell immune response in the progress of Plasmodium infection.

Integrated Network Pharmacology Analysis and Serum Metabolomics to Reveal the Anti-malaria Mechanism of Artesunate

“…Mice livers and spleens were fixed in 4% paraformaldehyde at room temperature for ≥24 h. After paraffin embedding and slicing, HE staining was performed to determine changes of hepatic and splenic architectures. 53 4.5. UHPLC-MS/MS-Based Serum Metabolomics.…”

γδ T‐cell–mediated immune responses to malaria

“…59 Not only splenic γδ T cells, but also lungresident γδ T cells could produce multiple cytokines including IL-4, IL-5, IL-6, IL-21, IL-1α, and IL-17, and lower levels of IFN-γ during P. yoelii infection. 69 Cohort studies in malaria endemic areas suggested that IFN-γ production was involved in both clinical immunity 66 and severe malaria. 66,70 γδ T cells produce large amounts of TNF and its production was associated with disease severity.…”

Experimental Models to Study the Pathogenesis of Malaria-Associated Acute Respiratory Distress Syndrome

“…Besides the conventional T cells that express CD4 + or CD8 + , there is a minor population of innate lymphocytes, known as gamma delta T cells (γδ T cells), that are also found in the lung during MA-ARDS ( Wei et al., 2021 ). These cells are known to respond to antigen without presentation ( Lawand et al., 2017 ).…”

“…Using γδ T cells-deficient mice infected with P. yoelii , lung injury still ensued despite the decrease in absolute number of total CD3 + cells including, CD4 + and CD8 + T cells. On the other hand, the percentage of IFN-γ-expressing CD3 + and CD8 + cells were higher in infected- γδ T deficient mice compared to WT mice ( Wei et al., 2021 ). Even though γδ T cells contribute to T cell immune response in the lung of Plasmodium -infected mice, further studies are needed to understand their role in MA-ARDS development.…”