Susanne Nylén Project

Immune modulation by eukaryotic parasites

We want to understand how regulatory immune responses induced by chronic infections and co-infections affect the ability to control intracellular pathogens of macrophages (e.g. Mycobacteria and Leishmania) and the implications this has on development of immunity.

Approximately 25% of the world’s population is infected with one or more parasitic worms, associated with delay in development and health decline. Most helminths dwell in the gut of their host. From an immunological perspective the most evident effects of such infestation are observed in the local microenvironment, but distal effects of gastrointestinal worm infestation, while implicated, are less well characterized. We postulate that helmith infections inhibit immunity to live vaccines and intracellular pathogens. Our research aims to understand the effect of concurrent chronic helminth infection on priming and recall responses to mycobacteria and Leishmania at sites both distal and proximal to worm infection. We strive to find mechanisms behind worm-mediated alterations of immune responses to vaccines and co-infecting pathogens and determine how de-worming affects such mechanisms and the outcome of the vaccination/ co-infection.

Leishmaniasis is the second most important parasitic disease world-wide. Peripheral blood mononuclear (PBMC) cells from patients with active visceral leishmaniasis (VL), the most severe form of leishmaniasis, typically fail to respond to Leishmania antigen when stimulated in vitro.  Paradoxically human VL is associated with upregulation of multiple pro-inflammatory cytokines and chemokines in plasma and increased transcriptional levels of IFN-gamma mRNA in lesional tissue such as the spleen.  While PBMC fail to respond, we have recently discovered that antigen specific responses can be detected in whole blood cultures.  Our findings suggest that unfavorable clinical outcomes are not related to an intrinsic Th1 response defect per se, but that other mechanisms contribute to parasite persistence and the pathogenesis of VL. In conclusions we want to identify and block immune responses that facilitate parasite persistence to enhance the paracitocidal immune response and promote cure.

Selected Publications

Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells.
Baptista M, Keszei M, Oliveira M, Sunahara K, Andersson J, Dahlberg C, et al
Nat Commun 2016 Jul;7():12175

Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut.
Obieglo K, Feng X, Bollampalli V, Dellacasa-Lindberg I, Classon C, Österblad M, et al
J. Immunol. 2016 Mar;196(5):2262-71

BCG Skin Infection Triggers IL-1R-MyD88-Dependent Migration of EpCAMlow CD11bhigh Skin Dendritic cells to Draining Lymph Node During CD4+ T-Cell Priming.
Bollampalli V, Harumi Yamashiro L, Feng X, Bierschenk D, Gao Y, Blom H, et al
PLoS Pathog. 2015 Oct;11(10):e1005206

Leishmania specific CD4 T cells release IFNγ that limits parasite replication in patients with visceral leishmaniasis.
Kumar R, Singh N, Gautam S, Singh O, Gidwani K, Rai M, et al
PLoS Negl Trop Dis 2014 Oct;8(10):e3198

Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis.
Cheuk S, Wikén M, Blomqvist L, Nylén S, Talme T, Ståhle M, et al
J. Immunol. 2014 Apr;192(7):3111-20

CD8 T cell exhaustion in human visceral leishmaniasis.
Gautam S, Kumar R, Singh N, Singh A, Rai M, Sacks D, et al
J. Infect. Dis. 2014 Jan;209(2):290-9

Tissue damage and immunity in cutaneous leishmaniasis.
Nylén S, Eidsmo L
Parasite Immunol. 2012 Dec;34(12):551-61

Immunobiology of visceral leishmaniasis.
Kumar R, Nylén S
Front Immunol 2012 ;3():251

Immunological perspectives of leishmaniasis.
Nylén S, Gautam S
J Glob Infect Dis 2010 May;2(2):135-46

Interleukin-10 and the pathogenesis of human visceral leishmaniasis.
Nylén S, Sacks D
Trends Immunol. 2007 Sep;28(9):378-84

Human visceral leishmaniasis is not associated with expansion or accumulation of Foxp3+ CD4 cells in blood or spleen.
Maurya R, Kumar R, Prajapati V, Manandhar K, Sacks D, Sundar S, et al
Parasite Immunol. 2010 Jul;32(7):479-83

Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis.
Nylén S, Maurya R, Eidsmo L, Manandhar K, Sundar S, Sacks D
J. Exp. Med. 2007 Apr;204(4):805-17

Project Members

Senior researcher

Susanne Nylén

Phone: 08-524 867 36
Organizational unit: Mats Wahlgren group

Graduate Student

Xiaogang Feng

Organizational unit: Mats Wahlgren group

PhD student

Cajsa Classon

Organizational unit: Mats Wahlgren group

Graduate Student

Graciela Teran

Organizational unit: Department of Microbiology, Tumor and Cell Biology (MTC), C1