Susanne Nylén Group
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.
Immune modulation by eukaryotic parasites
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.
IL-2 is an upstream regulator of CD4+ T cells from visceral leishmaniasis patients with therapeutic potential.
Chauhan S, Faleiro R, Kumar R, Ng S, Singh B, Singh O, et al
J. Infect. Dis. 2019 Feb;():
Intestinal nematode infection exacerbates experimental visceral leishmaniasis.
Classon C, Feng X, Eidsmo L, Nylén S
Parasite Immunol. 2019 Apr;41(4):e12618
Atrophy of skin-draining lymph nodes predisposes for impaired immune responses to secondary infection in mice with chronic intestinal nematode infection.
Feng X, Classon C, Terán G, Yang Y, Li L, Chan S, et al
PLoS Pathog. 2018 05;14(5):e1007008
Resident T Cells in Resolved Psoriasis Steer Tissue Responses that Stratify Clinical Outcome.
Gallais Sérézal I, Classon C, Cheuk S, Barrientos-Somarribas M, Wadman E, Martini E, et al
J. Invest. Dermatol. 2018 08;138(8):1754-1763
Differences in Nutritional and Health Status in School Children from the Highlands and Lowlands of Bolivia.
Terán G, Cuna W, Brañez F, Persson K, Rottenberg M, Nylén S, et al
Am. J. Trop. Med. Hyg. 2018 01;98(1):326-333
Immunogenicity is preferentially induced in sparse dendritic cell cultures.
Nasi A, Bollampalli V, Sun M, Chen Y, Amu S, Nylén S, et al
Sci Rep 2017 03;7():43989
A CFSE-based Assay to Study the Migration of Murine Skin Dendritic Cells into Draining Lymph Nodes During Infection with Mycobacterium bovis Bacille Calmette-Guérin.
Bollampalli V, Nylén S, Rothfuchs A
J Vis Exp 2016 10;(116):
A Subset of Neutrophils Expressing Markers of Antigen-Presenting Cells in Human Visceral Leishmaniasis.
Sharma S, Davis R, Srivastva S, Nylén S, Sundar S, Wilson M
J. Infect. Dis. 2016 11;214(10):1531-1538
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 07;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