Early Production of IL-22 but Not IL-17 by Peripheral Blood Mononuclear Cells Exposed to live Borrelia burgdorferi: The Role of Monocytes and Interleukin-1

If insufficiently treated, Lyme borreliosis can evolve into an inflammatory disorder affecting skin, joints, and the CNS. Early innate immunity may determine host responses targeting infection. Thus, we sought to characterize the immediate cytokine storm associated with exposure of PBMC to moderate levels of live Borrelia burgdorferi. Since Th17 cytokines are connected to host defense against extracellular bacteria, we focused on interleukin (IL)-17 and IL-22. Here, we report that, despite induction of inflammatory cytokines including IL-23, IL-17 remained barely detectable in response to B. burgdorferi. In contrast, T cell-dependent expression of IL-22 became evident within 10 h of exposure to the spirochetes. This dichotomy was unrelated to interferon-γ but to a large part dependent on caspase-1 and IL-1 bioactivity derived from monocytes. In fact, IL-1β as a single stimulus induced IL-22 but not IL-17. Neutrophils display antibacterial activity against B. burgdorferi, particularly when opsonized by antibodies. Since neutrophilic inflammation, indicative of IL-17 bioactivity, is scarcely observed in Erythema migrans, a manifestation of skin inflammation after infection, protective and antibacterial properties of IL-22 may close this gap and serve essential functions in the initial phase of spirochete infection

Disseminated disease due to non-tuberculous mycobacteria in HIV positive patients: a retrospective case control study

Introduction Disseminated infection due to non-tuberculous mycobacteria has been a major factor of mortality and comorbidity in HIV patients. Until 2018, U.S. American guidelines have recommended antimycobacterial prophylaxis in patients with low CD4 cell counts, a practice that has not been adopted in Europe. This study aimed at examining the impact of disseminated NTM disease on clinical outcome in German HIV patients with a severe immunodeficiency. Materials and methods In this retrospective case control study, HIV patients with disseminated NTM disease were identified by retrospective chart review and matched by their CD4 cell counts to HIV patients without NTM infection in a 1:1 alocation. Primary endpoints were mortality and time to first rehospitalisation. In addition, other opportunistic diseases, as well as antimycobacterial and antiretroviral treatments were examined. Results Between 2006 and 2016, we identified 37 HIV patients with disseminated NTM disease. Most of them were suffering from infections due to M. avium complex (n = 31, 77.5%). Time to event analysis showed a non-significant trend to higher mortality in patients with disseminated NTM disease (p = 0.24). Rehospitalisation took place significantly earlier in patients with disseminated NTM infections (median 40.5 days vs. 109 days, p<0.0001). Conclusion In this retrospective case control study, we could demonstrate that mortality is not significantly higher in HIV patients with disseminated NTM disease in the ART era, but that they require specialised medical attention in the first months following discharge