Innate and adaptive immune responses in HCV infections 

Markus H. Heim1,2,⇑ , Robert Thimme3,⇑ 1 Division of Gastroenterology and Hepatology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland; 2 Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland; 3 Department of Medicine, Clinic for Gastroenterology, Hepatology, Endocrinology, Infectious Diseases, University Hospital Freiburg, Freiburg, Germany 

PathCo is split into 5 basic research areas encompassing

the following objectives

-> To define the genetic and molecular basis underlying

TB regulation of HIV-1 replication

-> To define the role of HIV-1 infection and associated

inflammation on HCV replication

-> To identify common pathways defining Malaria

and HCV liver tropism

-> To generate humanized mouse model systems

that support pathogen co-infections

-> To identify the effect(s) of HIV-1 infection on HCV

specific host immune responses

The PathCo project brings together powerful multidisciplinary technologies that will improve our

understanding of the complex interactions between infectious agents and the host immune response that will significantly improve the management of co-infection associated disease.

 Recent developments in each of the disease disciplines enable the design of model systems that support pathogen co-infection, highlighting the timeliness of PathCo’s mission to study

the biological and immunological consequences of co-infection(s). Ultimately such knowledge will be instrumental in the rational design of new therapies and vaccines to control HIV-1, TB, malaria and HCV.

 In parallel to generating and utilizing new tools to understand the basic biology of pathogen co-interactions the PathCo consortium members will develop novel anti-microbials for translational research. 

The PathCo project will identify new targets for therapy and vaccine design, whilst validating known agents for their ability to block pathogen transmission and to target antigen or anti-pathogen components to dendritic cells (DCs).

PATHOGEN CO-INFECTION - THE PROBLEM

Acquired immune deficiency (AIDS), tuberculosis (TB) and malaria are the primary infectious diseases causing death worldwide. TB is responsible for a third to a half of human immunodeficiency virus type 1 (HIV-1)-associated deaths, particularly in sub Saharan Africa and South East Asia. Malaria is widely spread in tropical Africa and accounts for approximately 800,000 deaths every year. In addition to these pathogens, 170 million people are infected with hepatitis C virus (HCV), which leads to chronic liver disease. Because of shared routes of transmission, HCV co-infection is recognized as a major cause of morbidity and mortality among

HIV-1 infected persons.

The epidemiology and clinical features of co-infected subjects is well documented, however, there is a paucity of basic scientific studies addressing the interactions between these pathogens. There is undoubtedly a complex interplay between pathogens and the host

immune response.

PATHCO FOCUS AND OUTCOME

PathCo consortium proposes that pathogen evasion and dysregulation of host immune responses play a key role in co-infection associated morbidity. Within this Project will test this hypothesis by developing in vitro and ex vivo co-infection model systems to study co-pathogen interactions. The specific objectives of PathCo are to improve our understanding of pathogen

co-infection effect(s) on host innate and adaptive immune responses and to develop new approaches to dissect pathogen interactions: ranging from the genesis of fluorescent labelled viruses to state-of-the-art tissue explant culture systems and novel humanised mouse

models. Translational studies of infected subjects will define pathogen-specific effects on host immune responses and consequences for disease progression.

It is imperative that such interactions are elucidated before evaluating new prophylactic or therapeutic strategies in co-infected individuals.

PATHCO ALLIANCE

The PathCo consortium consists of nine beneficiaries from four EU different countries (UK, France, Germany and Italy) and one beneficiary from non-EU countries (South Africa).

PathCo is a well-balanced team of immunologists, virologists, clinicians, statisticians, epidemiologists with expertise in HIV/AIDS, TB, malaria and hepatitis C infection research and has the most appropriate scientific and technical background as well as the animal models and instrumentation required to fulfill the goals of this project and to succeed in its mission.

PathCo beneficiaries will have access to well-characterised established cohorts of co-infected patients from different geographical locations.

Technology

In vitro

systems

Advanced

Animal

Models

Human

Immunology

HIV

TB

HIV

HCV

HIV

Malaria

TB

regulation of

HIV replication

TB

regulation of

HIV replication

HIV infectioninflammation

in HCV

replication

Generation

humanized

mouse models

for mono- and

co-infection

HIV infection

on HCV

specific host

immune

responses

Common

pathways

of Malaria and

HCV entry into

hepatocytes

infection

Generation

humanized

mouse models

for mono- and

co-infection

PROJECT ORGANIZATION

pathogen Co-infection:

HIV-1, Tuberculosis, Malaria and hepatitis C virus

University of Birmingham

Jane McKeating - Gurdyal Besra

United Kingdom

www.birmingham.ac.uk

institUt nationaL de La santé

et de La reCherChe médiCaLe

Olivier Silvie - France

www.inserm.fr

UniversitaetskLinikUm freiBUrg

Robert Thimme - Germany

www.uniklinik-freiburg.de

University of oxford

Tao Dong - United Kingdom

www.ox.ac.uk

imperiaL CoLLege of sCienCe,

teChnoLogy and mediCine

Carolina Herrera - Xiao-Ning Xu

United Kingdom- www3.imperial.ac.uk

University of Cape toWn

Robert Wilkinson - South Africa

www.uct.ac.za

institut pasteur

James Di Santo - France

www.pasteur.fr

aLta riCerCa e sviLUppo

in BioteCnoLogie s.r.L.U.

Riccardo Bertini - Italy

www.altaweb.eu

PATHCO PARTNERS

pathogen Co-infeCtion:

HIV-1, Tuberculosis, Malaria

and hepatitis C virus

Coordinator:

Prof William a paxton phd diC

Department of Clinical Infection,

Microbiology and Immunology

Institute of Infection and Global Health

University of Liverpool

216e, Ronald Ross Building

8 West Derby Street

Liverpool L69 7BE

w.a.paxton@liverpool.ac.uk

www.pathco.org

EC Contribution: € 5.909.690

Duration: 60 months

Starting date: 01/11/2012

University of LiverpooL

Bill Paxton - United Kingdom

www.liv.ac.uk