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

TitleInterdependence between Interleukin-1 and Tumor Necrosis Factor Regulates TNF-Dependent Control of Mycobacterium tuberculosis Infection.
Publication TypeJournal Article
Year of Publication2015
AuthorsDi Paolo NC, Shafiani S, Day T, Papayannopoulou T, Papayannoupoulou T, Russell DW, Iwakura Y, Sherman D, Urdahl K, Shayakhmetov DM
JournalImmunity
Volume43
Issue6
Pagination1125-36
Date Published2015 Dec 15
ISSN1097-4180
KeywordsAnimals, 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
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.

DOI10.1016/j.immuni.2015.11.016
Alternate JournalImmunity
PubMed ID26682985
PubMed Central IDPMC4685953
Grant ListAI065429 / 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