Interdependence between Interleukin-1 and Tumor Necrosis Factor Regulates TNF-Dependent Control of Mycobacterium tuberculosis Infection.
|Title||Interdependence between Interleukin-1 and Tumor Necrosis Factor Regulates TNF-Dependent Control of Mycobacterium tuberculosis Infection.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Di Paolo NC, Shafiani S, Day T, Papayannopoulou T, Papayannoupoulou T, Russell DW, Iwakura Y, Sherman D, Urdahl K, Shayakhmetov DM|
|Date Published||2015 Dec 15|
|Keywords||Animals, Cell Separation, Disease Models, Animal, Flow Cytometry, Fluorescent Antibody Technique, Interleukin-1alpha, Mice, Mice, Inbred C57BL, Mice, Knockout, Mycobacterium tuberculosis, Receptors, Interleukin-1 Type I, Tuberculosis, Tumor Necrosis Factor-alpha|
The interleukin-1 receptor I (IL-1RI) is critical for host resistance to Mycobacterium tuberculosis (Mtb), yet the mechanisms of IL-1RI-mediated pathogen control remain unclear. Here, we show that without IL-1RI, Mtb-infected newly recruited Ly6G(hi) myeloid cells failed to upregulate tumor necrosis factor receptor I (TNF-RI) and to produce reactive oxygen species, resulting in compromised pathogen control. Furthermore, simultaneous ablation of IL-1RI and TNF-RI signaling on either stroma or hematopoietic cells led to early lethality, indicating non-redundant and synergistic roles of IL-1 and TNF in mediating macrophage-stroma cross-talk that was critical for optimal control of Mtb infection. Finally, we show that even in the presence of functional Mtb-specific adaptive immunity, the lack of IL-1α and not IL-1β led to an exuberant intracellular pathogen replication and progressive non-resolving inflammation. Our study reveals functional interdependence between IL-1 and TNF in enabling Mtb control mechanisms that are critical for host survival.
|PubMed Central ID||PMC4685953|
|Grant List||AI065429 / AI / NIAID NIH HHS / United States |
AI076327 / AI / NIAID NIH HHS / United States
R01 AI065429 / AI / NIAID NIH HHS / United States
AI107960 / AI / NIAID NIH HHS / United States
R01 AI076327 / AI / NIAID NIH HHS / United States
U19 AI106761 / AI / NIAID NIH HHS / United States
R01 AI107960 / AI / NIAID NIH HHS / United States