Priority Research Area Infections

Coinfection

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Tuberculosis (Tb) still is the most prevalent bacterial infectious disease in humans and continues to be a major cause of morbidity and mortality in impoverished regions in the tropics. The causative agent, Mycobacterium tuberculosis is carried by an estimated 2-3 billion people globally, but in most cases it lies dormant and the immune system is able to prevent it from spreading in the body. A relatively small proportion (5–10%) of infected people will develop active disease during their lifetime. However the immune system fails to achieve sterile eradication of the tubercle bacillus. The enormous reservoir of latent Tb patients constantly leads to new active Tb cases and transmission of the disease, thus perpetuating the epidemic. Reactivation can occur after years or decades of clinical latency, and the risk of reactivation increases with conditions that modulate the immune status of the host such as immunosuppressive therapy, malnutrition or comorbidities. The Research group Coinfection is interested in risk factors that promote active Tb or exacerbate the course of disease and focuses on coinfections as potential risk factors. Coinfections naturally occur due to the geographic overlap of distinct types of pathogenic organisms. Deviated immune responses in the context of coinfection can not only affect the outcome of disease but may also interfere with diagnosis and anti-infective interventions. We use experimental models of mixed infections to study disease outcome and vaccination in the context of coinfection. Our main focus is to investigate how concurrent parasitic or viral infections impact on the pathogenesis and immune control of Tb.

Another potential risk factor for Tb disease is the male sex. Globally, Tb notification data show a male-to-female ratio of 2:1 and higher. The excess of male Tb cases is seen worldwide in adult HIV-negative populations, but not in children and young adolescents. While socioeconomic and cultural factors have been regarded as responsible for the bias (undernotification, quality of sputum samples, access to health care, smoking, alcohol, drug use), biological factors may contribute significantly to the difference in susceptibility. Animal models may help to clarify the issue of genuine biological differences.

Our current research focuses on:

• The modulation of immune control of Tb in the context of malaria coinfection: We combine our infection model for Tb with different infection models for malaria (Plasmodium berghei, Plasmodium yoelii) in order to investigate the mutual influence of both diseases in the coinfected host.
• The efficacy and safety of live-attenuated malaria vaccines in the presence of M. tuberculosis or BCG: Preliminary data indicate impaired efficacy of live-attenuated malaria vaccines in M. tuberculosis infected mice. In a DFG-funded project, we want to unravel the immunological basis for impaired vaccine efficacy.
• The impact of influenza coinfection on Tb: Epidemiological data show that people with underlying respiratory conditions are at high risk of developing influenza-related complications. Influenza might be of particular risk for Tb patients. We investigate how an influenza coinfection influences M. tuberculosis specific immunity and pathology in the lungs.
• Male sex as risk factor for Tb: We apply our in vivo Tb infection model and combine it with in vitro examinations of selected cell populations (focus on macrophages) to identify biological factors that account for differences in Tb susceptibility between males and females.
• The modulation of cellular function by (co-) infection (myeloid-derived suppressor cells, macrophages and dendritic cells).