Biology subjects

Marshall, A. J.

Publications and source records attributed to Marshall, A. J..

3 recordsLinked to original sources

bioRxiv2022

MAIT cells activate dendritic cells to promote T follicular helper cell differentiation and humoral immunity

Protective immune responses against respiratory pathogens, including influenza virus are initiated by the mucosal immune system. However, most licensed vaccines are administered parenterally and are largely ineffective at inducing mucosal immunity. The development of safe and effective mucosal vaccines has largely been hampered by the lack of a suitable mucosal adjuvant. In this study we explore a novel class of adjuvant that harness mucosal-associated invariant T (MAIT) cells. We show evidence that intranasal immunisation of MAIT cell agonists co-administered with protein, including haemagglutinin from influenza A virus induced potent humoral immunity and immunoglobulin (Ig)A production, which protected mice against infection. MAIT cell adjuvant activity was mediated by CD40L-dependent activation of dendritic cells and subsequent priming of CD4+ T follicular helper cells. In summary, we show that MAIT cells are promising vaccine targets that can be utilised as cellular adjuvants in mucosal vaccines.

immunology↗

bioRxiv2021

Tafazzin deficiency in mouse mesenchymal stem cells potentiates their immunosuppression and impairs activated B lymphocyte immune function

Barth Syndrome (BTHS) is a rare X-linked genetic disorder caused by mutation in the TAFAZZIN gene which encodes the cardiolipin (CL) transacylase tafazzin (Taz). Taz deficiency in BTHS patients results in reduced CL in their tissues and a neutropenia which contributes to the risk of infections. However, the impact of Taz deficiency in other cells of the immune system is poorly understood. Mesenchymal stem cells (MSCs) are well known for their immune inhibitory function. We examined whether Taz-deficiency in murine MSCs impacted their ability to modulate lipopolysaccharide (LPS)-activated wild type (WT) murine B lymphocytes. MSCs from tafazzin knockdown (TazKD) mice exhibited a 50% reduction in CL compared to wild type (WT) MSCs. However, mitochondrial oxygen consumption rate and membrane potential were unaltered. In contrast, TazKD MSCs exhibited increased glycolysis compared to WT MSCs and this was associated with elevated proliferation, phosphatidylinositol-3-kinase expression and expression of the immunosuppressive markers indoleamine-2,3-dioxygenase, cytotoxic T-lymphocyte-associated protein 4, interleukin-10, and cluster of differentiation 59. When co-cultured with LPS-activated WT B cells, TazKD MSCs inhibited B cell proliferation and growth rate and reduced B cell secretion of IgM to a greater extent than B cells co-cultured with WT MSCs. In addition, co-culture of LPS-activated WT B cells with TazKD MSCs induced B cell differentiation toward potent immunosuppressive phenotypes including interleukin-10 secreting plasma cells and B regulatory cells compared to activated B cells co-cultured with WT MSCs. These results indicate that Taz deficiency in MSCs enhances MSCs-mediated immunosuppression of activated B lymphocytes.

immunology↗

bioRxiv2020

Extreme ecological specialization in a rainforest mammal, the Bornean tufted ground squirrel, Rheithrosciurus macrotis

The endemic Bornean tufted ground squirrel, Rheithrosciurus macrotis, has attracted great interest among biologists and the public recently. Nevertheless, we lack information on the most basic aspects of its biology. Here we present the first empirical data on the feeding ecology of tufted ground squirrels, and use data from 81 sympatric mammalian and avian vertebrates to place it within a broad comparative context. R. macrotis is a dedicated seed predator and shows much more extreme ecological specialization than any other vertebrate, feeding on a far smaller subset of available plant foods and demonstrating a greater reliance on a single plant species- Canarium decumanum-than any other vertebrate taxon. Our results suggest that R. macrotis plays an important, previously unknown role in the ecology of Bornean lowland forests, and highlight how much we have yet to learn about the fauna inhabiting some of the most diverse, and most severely threatened, ecosystems on the planet.

ecology↗