Infection and Immunity in Global Health

Bild: Susanne Dürr                            The group 2020

CGH / HelmVit

The consortial project HELMVIT (“Impact of maternal helminth infection on Vitamin D regulation and on the immune system of the infant”) was kicked-off in January 2019, in Lambaréné, Gabon. This project is coordinated by Prof. Clarissa Prazeres da Costa, Kodirector of the Center for Global Health, Institute for Medical Microbiology, Immunology and Hygiene of TUM and collaboration partners are Prof. Akim Adegnika (CERMEL) and Dr. Meral Esen (Institute for Tropical Medicine, University of Tübingen). The consortium is funded for three years by the DFG within the call “German-African Cooperation Projects in Infectiology”.

Click here for the HELMVIT Video

TUM Cairo: Launch of the German-Egyptian Network for Genomic Medicine and Population Health

Kick-off for the German Egyptian Network for Advancing Genomic Medicine and Population Health GE-GPx... read more

Autor: Prof. Dr. med. Clarissa Prazeres da Costa Portrait


Throughout his evolution, man has been parasitized by multicellular organisms, also called helminths or worms. This has led to an intriguing relationship between the immune system of the host and the parasite. The latter with its plethora of secreted molecules enables immune evasion and active suppression of host immune responses that ensures the survival of the parasiteandthe host How this is accomplished and what are the effects on other diseases (e.g. allergies, infectious diseases) are the main interests of our research group. We work with the parasiteSchistosoma mansoni, the causative agent of schistosomiasis (Billharzia), which is a chronic disease in developing countries with currently 200-300 million infected people worldwide. The complex life cycle is depicted in the figure below and is maintained in our institute:

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Host-pathogen interaction-the research topics within the group:

Immuneregulation and allergy development: Schistosomiasis elicits distinct immune responses within the host, ranging from an initial Th1 and subsequent Th2-phase to a regulatory state e.g. by the expansion of regulatory B and T cells and is associated with dampened allergic reactions within the host. The exact underlying mechanisms to achieve this fine-tuned immunebalance are still a matter of ongoing investigation. In this setting, one topic in the group is to investigate the role of regulatory T cells during infection and their effect on the development of allergic airway inflammation as well as immune suppressive features of schistosome antigens.

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Co-infection: One of the main complications of acute Hepatitis B virus infection (HBV) is the development of a chronic infection. Interestingly, chronicity develops at a higher frequency in developing countries in which co-infections with several helminth species, such as S. mansoni, are common. The underlying mechanisms leading to HBV chronicity are only partly understood but effective CD8+ and CD4+ T cell responses could be compromised in helminth co-infected patients.In close collaboration with the Institute of Virology (Head: Prof. U. Protzer) we are currently investigating the influence of concomitant schistosome infection on acute and chronic hepatitis B in mouse models with a focus on the cellular processes and immune responses within the liver.

Another co-infection topic within the group is the bacterium H.pylori. The pathogen chronically persists in the stomach of individuals and can cause varying disease outcomes ranging from chronic gastritis to gastric and duodenal ulcers as well as gastric cancer. Due to the immunomodulatory abilities of helminths, we propose that a concurrent helminth infection potentially drives the Th1 dominated H. pylori-specific immune response to a more protective Th-2 phenotype and thereby eventually influences cancer development. Underlying signaling pathways within the gastric mucosa altered by systemic helminth-driven, chronic immune responses are the focus within these studies performed in close collaboration with the group of Prof. M. Gerhard of the institute (MIH).

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Complement system: Besides the activation of the adaptive immune responses, we also investigate the role of the complement system as first line of defense of the innate immune system during schistosomiasis together with the group of Dr. A. Verschoor at the MIH using different knockout-models. Within these studies, we focus on the interaction between schistosomes and certain proteins of the classical complement pathway during infection and their impact on worm development, immune responses and survival. In addition, we investigate whether such complement factors influence the transformation process from free-living cercariae to the host stage schistosomula and their viability in vitro.  


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Schistosomiasis during pregnancy and transgenerational effects: Interestingly, in endemic areas people are infected very early in childhood or they are exposed to helminth antigens already in utero by the transfer of parasite antigens or immunological molecules via the placenta or breastmilk. Accordingly, one of our main interests is to evaluate how this non-transplacental helminth infection during pregnancy alters the offspring’s immune system development and/or allergen susceptibility later in life. Within these studies, we focus on the cytokine milieu and gene-expression within the feto-maternal unit of infected mothers and the early immune system composition in offspring from infected mothers, with a special focus on T cell differentiation capacity and hematopoiesis. Functionally, offspring are subjected to diverse immune challenge models such as OVA-induced allergic airway inflammation and infection models to assess their phenotype in more detail. The role of maternal candidate genes in shaping the offspring’s immune system is evaluated via diverse knockout mouse models.   picture 6


An anti-inflammatory eicosanoid switch mediates the suppression of type-2 inflammation by helminth larval products.

De los Reyes Jiménez M, Lechner A, Alessandrini F, Bohnacker S, Schindela S, Trompette A, Haimerl P, Thomas D, Henkel F, Mourão A, Geerlof A,Prazeres da Costa C, Chaker AM, Brüne B, Nüsing R, Jakobsson P, Nockher WA, Feige MJ, Haslbeck M, Ohnmacht C, Marsland BJ, Voehringer D, Harris NL, Schmidt-Weber CB, Esser-von

J. Sci Transl Med 2020 Apr 22;12(540):eaay0605. doi: 10.1126/scitranslmed.aay0605

Host immune responses during Taenia solium Neurocysticercosis infection and treatment.

Prodjinotho UF, Lema J, Lacorcia M, Schmidt V, Vejzagic N, Sikasunge C, Ngowi B, Winkler AS, Prazeres da Costa

CPLOS NTD Published: April 16, 2020

Placental gene expression and antibody levels of mother-neonate pairs reveal an enhanced risk for inflammation in a helminth endemic country.

Ludwig E, Harder J, Lacorcia M, Honkpehedji JY, Nouatin O, van Dam GJ, Corstjens PLAM, Sartono E, Esen M, Lobmaier SM, Adegnika AA, Prazeres da Costa C 

Sci Rep. 2019 Oct 31;9(1):15776.

Dynamic, helminth-induced immune modulation influences the outcome of acute and chronic hepatitis B virus infection.

Eva Loffredo-Verde E, Bhattacharjee S, Malo A, Hasreiter J, Kosinska A, Ringelhan M, Heikenwaelder M, Protzer U*, Clarissa U. Prazeres da Costa C*

J Infect Dis. 2019 Dec 25

Concomitant infection of S. mansoni and H. pylori promotes promiscuity of antigen experienced cells and primes the liver for a lower fibrotic response.

Bhattacharjee S, Loffredo-Verde, Toska A,  Flossdorf M, Mejías-Luque R, Gerhard M* and Prazeres da Costa C*.

Cell Rep. 2019 Jul 2;28(1):231-244.e5.

The 2017 Oslo conference report on neglected tropical diseases and emerging/re-emerging infectious diseases – focus on populations underserved.

Klohe K, Amuasi J, Kaducu JM, Haavardsson I, Bogatyreva E, Onarheim KH, Harrison W, Kristensen F, Prazeres da Costa C* and Winkler AS*.

Infectious Diseases of Poverty (2019) 8:40

A novel cell-free method to culture Schistosoma mansoni from cercariae to juvenile worm stages for in vitro drug testing.

Frahm S, Anisuzzaman DVM, Prodjinotho F, Vejzagić N, Verschoor A and Prazeres da Costa C;

PLOS NTD 2019 Jan 28;13(1): e0006590. doi: 10.1371

Antimicrobial resistance in livestock and poor quality veterinary medicines.

Clifford K, Desai D, Prazeres da Costa C, Meyer H, Klohe K, Winkler AS, Rahman T, Islam T, Zaman MH.

Bull World Health Organ. 2018 Sep 1;96(9):662-664. doi: 10.2471/BLT.18.209585. Epub 2018 Jul 16

Maternal helminth infections and the shaping of offspring immunity.

Dewals BG, Layland LE, Prazeres da Costa C, Horsnell WG

Parasite Immunol. 2018 Oct 29:e12599. doi: 10.1111/pim.12599

Maternal Schistosomiasis: Immunomodulatory Effects with Lasting Impact on Allergy and Vaccine Responses.

Lacorcia M and Prazeres da Costa C;

Front. Immunol. | doi: 10.3389/fimmu. 2018.02960

Positive phototropism is accelerated in Biomphalaria glabrata snails by infection with Schistosoma mansoni.

Maeda H, Hatta T, Tsubokawa D, Mikami F, Nishimaki T, Nakamura T, Anisuzzaman, Matsubayashi M, Ogawa M, da Costa CP, Tsuji N.

Parasitol Int. 2018 Jun 9;67(5):609-611. doi: 10.1016/j.parint.2018.06.003.

Dectin-1/2-induced autocrine PGE2 signaling licenses dendritic cells to prime Th2 responses.

Kaisar MMM, Ritter M, Del Fresno C, Jónasdóttir HS, van der Ham AJ, Pelgrom LR, Schramm G, Layland LE, Sancho D, Prazeres da Costa C, Giera M, Yazdanbakhsh M, Everts B.

PLoS Biol. 2018 Apr 18;16(4):e2005504.

Neglected tropical diseases - the present and the future.

Winkler AS, Klohe K, Schmidt V, Haavardsson I, Abraham A, Prodjinotho UF, Ngowi B, Sikasunge C, Noormahomed E, Amuasi J, Kaducu J, Ngowi H, Abele-Ridder B, Harrison WE, Prazeres da Costa C.

Tidsskr Nor Laegeforen. 2018 Jan 2;138(3)

First case of human peritoneal cysticercosis mimicking peritoneal carcinosis: necessity of laparoscopy and histologic assessment for the correct diagnosis.

Rudelius M, Brehm K, Poelcher M, Spinner C, Rosenwald A, da Costa CP.

JMM Case Rep. 2017 Jun 8;4(6)

Nutrition – A global challenge for health.

Klohe K, Prazeres da Costa C, Lien N, Holmboe-Ottesen G, Rychlik M, Haavardsson I, Stordalen G, Singh S, Engebretsen I, Iversen PO, Winkler AS.

Tidsskr Nor Laegeforen. 2017 Dec 12;137(23-24).

Chronic schistosomiasis during pregnancy epigenetically reprograms T cell differentiation in offspring of infected mothers.

Klar K, Perchermeier S, Bhattacharjee S, Harb H, Adler T, Istvanffy R, Loffredo-Verde E, Oostendorp R, Renz H, Prazeres da Costa C.

Eur J Immunol March 2017

Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity.

Roth S, Bergmann H, Jaeger M, Yeroslaviz A, Neumann K, Koenig PA, Prazeres da Costa C, Vanes L, Kumar V, Johnson M, Menacho-Márquez M, Habermann B, Tybulewicz VL, Netea M, Bustelo XR, Ruland J.

Cell Rep. 2016 Dec 6

Parasites, microbiota and metabolic disease.

Bhattacharjee S, Kalbfuss N, Prazeres da Costa C.

Parasite Immunol. 2016 Oct 7. doi: 10.1111/pim.12390.

Microbes and asthma: Opportunities for intervention.

Smits HH, Hiemstra PS, Prazeres da Costa C, Ege M, Edwards M, Garn H, Howarth PH, Jartti T, de Jong EC, Maizels RM, Marsland BJ, McSorley HJ, Müller A, Pfefferle PI, Savelkoul H, Schwarze J, Unger WW, von Mutius E, Yazdanbakhsh M, Taube C.

J Allergy Clin Immunol. 2016 Mar;137(3):690-7

An Unusual Presentation of Neurocysticercosis: A Space-Occupying Lesion in the Fourth Ventricle Associated with Progressive Cognitive Decline.

Kurz C, Schmidt V, Poppert H, Wilkins P, Noh J, Poppert S, Schlegel J, Delbridge C, da Costa CP, Winkler AS.

Am J Trop Med Hyg. 2016 Jan;94(1):172-5. doi: 10.4269/ajtmh.15-0099. Epub 2015 Nov 30.

Schistosome infection aggravates HCV-related liver disease and induces changes in the regulatory T cell phenotype.

Loffredo-Verde E, Abdel-Aziz I, Layland L, Busch DH, Prazeres da Costa C.

Parasite Immunol. 2015 Jan 5. doi: 10.1111/pim.12171.

Maternal helminth infections.

Straubinger K, Prazeres da Costa C.

Adv Exp Med Biol. Oct 2014;828:27-48

Helicobacter pylori-Induced IL-1beta Secretion in Innate Immune Cells Is Regulated by the NLRP3 Inflammasome and Requires the Cag Pathogenicity Island.

Semper, R.P., Mejias-Luque, R., Gross, C., Anderl, F., Muller, A., Vieth, M., Busch, D.H., Prazeres da Costa, C., Ruland, J., Gross, O., and Gerhard, M. 2014. 

J Immunol. doi: 10.4049/jimmunol.1400362.

T Cell-Derived IL-4/IL-13 Protects Mice against Fatal Schistosoma mansoni Infection Independently of Basophils

Schwartz C, Oeser K, Prazeres da Costa C, Layland LE, Voehringer D.

J Immunol. 2014 Oct 1;193(7):3590-9

Functional relevance of NLRP3 inflammasome-mediated IL-1bduring acute allergic airway inflammation.

Ritter M, Straubinger K, Schmidt S, Busch D, Hagner S, Garn H, Layland L, Prazeres da Costa

CClin Exp Immunol. 2014 Nov;178(2):212-23

Maternal Helminth Infection Determines Offspring Susceptibility to Allergic Airway Inflammation.

Straubinger K, Paul S, Prazeres da Costa O, Buch T, Busch DH, Layland L and Prazeres da Costa C.

J Allergy Clin Immunol. 2014Jul 18. pii: S0091-6749(14)00794-5

Lack of Host Gut Microbiota Alters Immune Responses and Intestinal Granuloma Formation during Schistosomiasis.

Holzscheiter M, Layland LE, Loffredo-Verde E, Mair K, Vogelmann R, Langer R, Wagner H, Prazeres da Costa C.

Clin Exp Immunol. 2013 Oct 30. doi: 10.1111/cei.12230.

Schistosoma mansoni-mediated Suppression of Allergic Airway Inflammation Requires Patency and Foxp3+ Treg Cells.

Layland LE, Straubinger K, Ritter M, Loffredo-Verde E, Garn H, Sparwasser T, Prazeres da Costa C.

PLOS NTD 2013 Aug 15;7(8):e2379

Fetal-maternal alignment of regulatory T cells correlates with Interleukin 10 and Bcl-2 upregulation in pregnancy.

Santner-Nanan B, Straubinger K, Hsu P, Parnell G, Tang B, Xu B, Makris A, Hennessy A, Peek M, Busch DH, Prazeres da Costa, Cand Nanan RJ

Immunol. 2013 Jul 1;191(1):145-153

The Mincle-activating Adjuvant TDB Induces MyD88-dependent Th1 and Th17 Responses through IL-1R signaling.  

Desel C, Werninghaus K, Ritter M, Jozefowski K, Wenzel J, Russkamp N, Schleicher U, Christensen D, Wirtz S, Kirschning C, Agger E,da Costa CP and Lang R.

PLoS One.2013;8(1): e53531

Molecular diagnosis of subcutaneous Spirometra erinaceieuropaeisparganosis in a Japanese immigrant.

Tappe D, Berger L, Haeupler A, Muntau B, Racz P, Harder Y, Specht K, Prazeresda Costa C,  Poppert S.

Am J Trop Med Hyg. 2013 Jan;88(1):198-202

Primary extrahepatic alveolar echinococcosis of the lumbar spine and the psoas muscle: A Case Report and Review of Literature.

Nell M, Burgkart RH, Gradl G, von Eisenhart-Rothe R, Schaeffeler C, Trappe D,Prazeres da Costa C, Gradinger R, Kirchhoff C.

Ann Clin Microbiol Antimicrob.2011 Apr 15;10(1):13

An imported case of external ophthalmomyiasis caused by the sheep botfly (Oestrus ovis) – case report.

Abdel-Aziz I, Layland LE, Prazeres da Costa C.

Sci Parasitologica. 2010 Dec 11;4: 207-211

Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses.

Ritter M, Gross O, Kays S, Ruland J, Nimmerjahn F, Saijo S, Tschopp J, Layland LE, Prazeres da Costa C.

Proc Natl Acad Sci U S A. 2010 Nov 8.

Pronounced phenotype in activated regulatory T cells during a chronic helminth infection.

Layland LE, Mages J, Loddenkemper C, Hoerauf A, Wagner H, Lang R,da Costa CU.

J Immunol. 2010 Jan 15;184(2):713-24. Epub 2009 Dec 9

Regulatory T cells primed in the absence of TLR2 fail to control Immunopathology and TH responses in Schistosomiasis.

Layland LE, Rad R, Wagner H,da Costa CU

Eur J Immunol. 2007 Aug;37(8):2174-84.

Multicystic tumor in the fourth ventricle: consider neurocysticercosis.Costa CU, von Einsiedel HG, Disko R, Berthele A.

J Neurol.2006 Aug;253(8):1092-3.

Helicobacter pylori-induced Foxp3+ regulatory T cells control anti-microbial Th1 immunity and favour chronic bacterial persistence in humans and mice.

Rad R, Brenner L, Bauer S, Schwendy S, Layland L,da Costa CP, Reindl W, Dossumbekova A, Friedrich M, Saur D, Wagner H, Schmid RM, Prinz C

Gastroenterology.2006 Aug;131(2):525-37

Lack of antigen-specific Th1 response alters granuloma formation and composition inSchistosoma mansoniinfected MyD88-deficient mice.

Layland L, Wagner H,Prazeres da Costa C

Eur J Immunol.2005 Nov;35(11):3248-57

Polymorphonuclear neutrophils improve replication of Chlamydia pneumoniae in vivo upon MyD88-dependent attraction.

Rodriguez N, Fend F, Jennen L, Schiemann M, Wantia N,Prazeres da Costa CU, Durr S, Heinzmann U, Wagner H, Miethke T.

J Immunol.2005 Apr 15;174(8):4836-44.

Heat shock protein 60 from Chlamydia pneumoniae elicits an unusual set of inflammatory responses via Toll-like receptor 2 and 4 in vivo.

da Costa CP, Wantia N, Busch D, Durr S,  Wagner H, Miethke T. Eur

J Immunol. 2004 Oct;34(10):2874-84.

The Gram-negative bacterium Chlamydia trachomatis L2 stimulates tumor necrosis factor secretion by innate immune cells independently of its endotoxin.

Prebeck S, Brade H, Kirschning CJ,da Costa CP, Durr S, Wagner H, Miethke T.

Microbes Infect. 2003 May;5(6):463-70.

Role of IgG-seropositivity to Chlamydia pneumoniae in early thrombotic events after coronary stent placement.

da Costa CP, Neumann FJ, Kastrati A, Stallforth I, Schmid M, Joghetai N, Prebeck S, Wagner H, Miethke T.

Atherosclerosis. 2003 Jan;166(1):171-6.)

The endoplasmic reticulum-resident heat shock protein Gp96 activates dendritic cells via the Toll-like receptor 2/4 pathway.

Vabulas RM, Braedel S, Hilf N, Singh-Jasuja H, Herter S, Ahmad-Nejad P, Kirschning CJ, Da Costa C, Rammensee HG, Wagner H, Schild H.

J Biol Chem. 2002 Jun 7;277(23):20847-53.

Chlamydia pneumoniae activates IKK/I kappa B-mediated signaling, which is inhibited by 4-HNE and following primary exposure.

Donath B, Fischer C, Page S, Prebeck S, Jilg N, Weber M,da Costa C, Neumeier D, Miethke T, Brand K.

Atherosclerosis. 2002 Nov;165(1):79-88.

Role of chlamydial heat shock protein 60 in the stimulation of innate immune cells by Chlamydia pneumoniae.

da Costa CP, Kirschning CJ, Busch D, Durr S, Jennen L, Heinzmann U, Prebeck S, Wagner H, Miethke T.

Eur J Immunol. 2002 Sep;32(9):2460-70.

Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells.

Vabulas RM, Ahmad-Nejad P, da Costa C, Miethke T, Kirschning CJ, Hacker H, Wagner H.

J Biol Chem. 2001 Aug 17;276(33):31332-9. 2001 Jun 11.

Predominant role of toll-like receptor 2 versus 4 in Chlamydia pneumoniae-induced activation of dendritic cells.

Prebeck S, Kirschning C, Durr S,da Costa C, Donath B, Brand K, Redecke V, Wagner H, Miethke T.

J Immunol. 2001 Sep 15;167(6):3316-23.

Treatment of Chlamydia pneumoniae infection with roxithromycin and effect on neointima proliferation after coronary stent placement (ISAR-3): a randomised, double-blind, placebo-controlled trial.

Neumann F, Kastrati A, Miethke T, Pogatsa-Murray G, Mehilli J, Valina C, Jogethaei N,da Costa CP, Wagner H, Schomig A.

Lancet. 2001 Jun 30;357(9274):2085-9.

Picture 1: phospholipids within schistosome egg antigens, picture 2: confocal image of a live egg (shell+miracidium) in the intestine, picture 3: s. mansonieggs, picture 4: confocal image of villi and crypts during infection, picture 5: confocal image of villi and crypts during infection, picture 6: masson’s stained liver, picture 7: biomphalaria glabrata, picture 8: live schistosomulae