Interdependence between Interleukin-1 and Tumor Necrosis Factor Regulates TNF-Dependent Control of Mycobacterium tuberculosis Infection.

Abstract

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.

• Authors: Nelson C Di Paolo, Shahin Shafiani, Tracey Day, Thalia Papayannopoulou, Thalia Papayannoupoulou, David W Russell, Yoichiro Iwakura, David Sherman, Kevin Urdahl, Dmitry M Shayakhmetov
• Journal: Immunity (Immunity) Vol. 43 Issue 6 Pg. 1125-36 (Dec 15 2015) ISSN: 1097-4180 [Electronic] United States
• PMID: 26682985 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• IL1R1 protein, mouse
• Interleukin-1alpha
• Receptors, Interleukin-1 Type I
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Cell Separation
• Disease Models, Animal
• Flow Cytometry
• Fluorescent Antibody Technique
• Interleukin-1alpha (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mycobacterium tuberculosis
• Receptors, Interleukin-1 Type I (immunology)
• Tuberculosis (immunology)
• Tumor Necrosis Factor-alpha (immunology)