Novel role for IL-22 in protection during chronic Mycobacterium tuberculosis HN878 infection

Abstract

Approximately 2 billion people are infected with Mycobacterium tuberculosis (Mtb), resulting in 1.4 million deaths every year. Among Mtb-infected individuals, clinical isolates belonging to the W-Beijing lineage are increasingly prevalent, associated with drug resistance, and cause severe disease immunopathology in animal models. Therefore, it is exceedingly important to identify the immune mechanisms that mediate protection against rapidly emerging Mtb strains, such as W-Beijing lineage. IL-22 is a member of the IL-10 family of cytokines with both protective and pathological functions at mucosal surfaces. Thus far, collective data show that IL-22 deficient mice are not more susceptible to aerosolized infection with less virulent Mtb strains. Thus, in this study we addressed the functional role for the IL-22 pathway in immunity to emerging Mtb isolates, using W-Beijing lineage member, Mtb HN878 as a prototype. We show that Mtb HN878 stimulates IL-22 production in TLR2 dependent manner and IL-22 mediates protective immunity during chronic stages of Mtb HN878 infection in mice. Interestingly, IL-22-dependent pathways in both epithelial cells and macrophages mediate protective mechanisms for Mtb HN878 control. Thus, our results project a new protective role for IL-22 in emerging Mtb infections.

Interleukin-22 Induces the Infiltration of Visceral Fat Tissue by a Discrete Subset of Duffy Antigen Receptor for Chemokine-Positive M2-Like Macrophages in Response to a High Fat Diet

“…IL-22 is a tightly regulated pro-and anti-inflammatory member of the IL-10 family that signals through the IL-22 receptors, and is composed of a ubiquitous IL-10R2 subunit and a restrictively expressed IL-22R1 subunit [29,48]. Even though the primary role of immune cells, especially Th cells, is the production of IL-22, it is well-known that several immune cells can induce IL-22R1 under certain pathologic conditions such as mycobacterium infected macrophages [49,50] and leukemia [51]. Hence, it is perhaps unsurprising to find that IL-22R1 is expressed in certain mononuclear cell population in obese conditions.…”

Tissue‐resident innate immunity in the lung

“…They appear to be the most abundant ILC group in the human lung, 62 but studies highlighting the role of ILC3s in the lung are limited. 82 Both IL-22 and IL-17 are important in protecting mice from hypervirulent strains of M tuberculosis, 85,86 and IL-22 from CD3 À CD56 + ILC3-like cells inhibits M. tuberculosis growth through enhanced phagolysosomal fusion. 81 ILC3s are in fact the major producers of IL-22 in the lung, 82,83 and consequently are probably important for tissue repair following viral infection.…”

“…Indeed, boosting of IL-22 production by exogenous administration of flagellin allowed mice to clear an otherwise lethal infection. 82 Both IL-22 and IL-17 are important in protecting mice from hypervirulent strains of M tuberculosis, 85,86 and IL-22 from CD3 À CD56 + ILC3-like cells inhibits M. tuberculosis growth through enhanced phagolysosomal fusion. 87 Consistent with this, we recently showed that ILC3s play an important role in the immune response to M. tuberculosis infection.…”

Th1 cytokines, true functional signatures for protective immunity against TB?

“…Elnaggar et al 42 Kathamuthu et al 43 Wang et al 44 Mayer-Barber et al 45 Mayer-Barber Hu et al 47 Wozniak et al 48 Ahmed et al 49 Pereira et al 50 Heidarnezhad et al 51 You et al 52 Wang et al 53 Xu et al 54 Zhao et al 55 Gopal et al 56 Treerat et al 57…”