Forschungszentrum Borstel
Forschungszentrum Borstel

Priority Research Area Infections

Infection Immunology

Fig.1. Reactivation of a Mtb infection in the mouse
Reactivation of a Mtb infection in the mouse
Fig.2. Granuloma necrosis in the lung upon reactivation of a Mtb infection
Granuloma necrosis in the lung upon reactivation of a Mtb infection


Infectious diseases are the leading cause of death worldwide and the number of deaths from infectious diseases has been increasing. The wide use of effective antibiotics, the potential for universal immunization for many childhood illnesses, and success stories such as the imminent eradication of polio encouraged the perception that infectious diseases are no longer a public health threat. However, even as some previously epidemic infectious diseases have been controlled, new diseases emerge and old diseases rebound, sometimes in drug-resistant forms. These events increasingly challenge basic research on the immunology of infectious diseases aiming at a better understanding of mechanisms involved in protection and pathology.

Infection with many intracellular pathogens results in persistence of the pathogen and chronic disease. These pathogens include Trypanosoma cruzi, the causative agent of American trypanosomiasis or Chagas disease. The immune system of the human host is capable of mounting an adequate cell-mediated inflammatory immune response against these intracellular pathogens. However, during persisting chronic infectious diseases cell-mediated inflammatory reactions may also be detrimental to the host leading to reactivation (Figure 1) and pathology (Figure 2). We want to understand the cytokine-mediated regulation of protection, persistence and pathology in order to dissect protective and pathology-promoting mechanisms associated with the inflammatory response during chronic infectious diseases. To disclose immune mechanisms involved in controlling or reactivating persistent infections, we are analyzing cytokine-mediated regulation of protection, persistence and pathology in genetically modified mice after infection with the above pathogens. Many cytokines differentially act on different cell types. Therefore, we are studying infectious diseases especially in cell type-specific gene-deficient animals. By differential gene expression analysis in infected cell type-specific gene-deficient vs. wild type mice we further want to identify novel genes involved in regulation protection, persistence and pathology during chronic infectious diseases.

One main area of our research is the fine-tuning of infection-induced inflammatory immune responses by the gp130 family cytokines Interleukin (IL)-6, IL-6/IL-6R, IL-12, IL-12p80, IL-23, IL-27, Epstein Barr virus-induced protein 3 (EBI3) and IL-35. We found that IL-6/IL-23-driven T helper (TH)17 cells are critical for maintaining protective TH1 immune responses during chronic infection. On the other hand, we could shown that IL-27 can modulate excessive TH17 inflammation by suppressing activated myeloid cells and both prevents optimal anti-microbial protection and limits the pathological sequelae of chronic inflammation. Further analysis will unravel the TH17-dependent mechanisms mediated e.g. by IL-17, IL-21 or IL-22.

A second focus of our research is the regulation of protection and immunopathology during infectious diseases by the type 2 cytokines IL-4 and IL-13 in vivo. We found that IL-4 receptor-alpha (Ra)-dependent mechanisms - most likely in alternatively activated macrophages - are involved in reactivation and granuloma necrosis during experimental tuberculosis and facilitate persistence during chronic T. cruzi infection. Currently, we are trying to disclose IL-4Ra downstream mechanisms that mediate persistence, reactivation and pathology during chronic infectious diseases.