Principal Investigator:

Impact of different macrophage subsets on
T cell responses and pathogen clearance
during Plasmodium yoelii infection

Our recent studies provide evidence that conventional DCs are important for efficient T cell activation in the initial phase of Plasmodium yoelii (P. yoelii) infection. However, T cells from P. yoelii-infected DC-depleted mice were still more activated than those from non-infected controls indicating that other antigen-presenting cells, such as macrophages, might contribute to T cell activation. This hypothesis is supported by elevated MHC-II expression on macrophages during P. yoelii infection. Splenic macrophages consist of three main subsets, namely red pulp macrophages, marginal zone macrophages and marginal metallophilic macrophages. Although some studies have already demonstrated a critical role of splenic macrophages for parasite clearance, results were controversial and the impact of different splenic macrophage subsets on pro- and anti-inflammatory T cell responses during P. yoelii infection remains unclear and is aimed to be analyzed in the proposed project.

Publications

Hose M, Günther A, Abberger H, Begum S, Korencak M, Becker KA, Buer J, Westendorf AM, Hansen W. T cell-specific overexpression of acid sphingomyelinase results in elevated T cell activation and reduced parasite burden during Plasmodium yoelii infection. Front Immunol 2019;10:1225.

Thiel J, Alter C, Luppus S, Eckstein A, Tan S, Führer D, Pastille E, Westendorf AM, Buer J, Hansen W. MicroRNA-183 and microRNA-96 are associated with autoimmune responses by regulating T cell activation. J Autoimmun 2019;96: 94-103.

Ueffing K, Abberger H, Westendorf AM, Matuschewski K, Buer J, Hansen W. Conventional CD11c^high dendritic cells are essential for T cell priming during the initial phase of Plasmodium yoelii infection, but are dispensable at later time points. Front Immunol 2017;8:1333.

Loevenich K, Ueffing K, Abel S, Hose M, Matuschewski K, Westendorf AM, Buer J, Hansen W. DC-derived IL-10 interferes with pro-inflammatory cytokine production and promotes induction of CD4+IL-10+ regulatory T cells during Plasmodium yoelii infection. Frontiers Immunol 2017;8: 152.

Abel S, Ueffing K, Tatura R, Hutzler M, Hose M, Matuschewski K, Kehrmann J, Westendorf AM, Buer J, Hansen W. Plasmodium yoelii infection of BALB/c mice results in expansion rather than induction of CD4+Foxp3+ regulatory T cells. Immunology 148: 197-205.

Jost NH, Abel S, Hutzler M, Sparwasser T, Zimmermann A, Roers A, Müller W, Hengel H, Westendorf, AM, Buer J, Hansen W. Regulatory T cells and T cell derived IL-10 interfere with effective anti-cytomegalovirus immune response. Immunol Cell Biol 2014;92:860-71.

Abel S, Lückheide N, Westendorf AM, Geffers R, Roers A, Muller W, Sparwasser T, Matuschewski K, Buer J, Hansen W. Strong impact of CD4+Foxp3+ regulatory T cells and limited effect of T cell-derived IL-10 on pathogen clearance during Plasmodium yoelii infection. J Immunol 2012;188:5467-77.

Hansen W, Hutzler M, Abel S, Alter C, Stockmann C, Kliche S, Albert J, Sparwasser T, Sakaguchi S, Westendorf AM, Schadendorf D, Buer J, Helfrich I. Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth. J Exp Med 2012;209:2001-16.