Role of interleukin-12 family cytokines in the cellular response to mycobacterial disease

Méndez-Samperio, Patricia

doi:10.1016/j.ijid.2009.06.022

Cited by 59 publications

(39 citation statements)

References 93 publications

(101 reference statements)

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“…Crosstalk between dendritic cells and Th cells is a critical process for Th cell differentiation, and it is mediated by various cytokines. Among them, IL-12 is essential for Th1 cell differentiation, whereas IL-6 and IL-23 play a key role in Th17 cell differentiation (3,48). TGF-b is required for both Th17 and regulatory T cell differentiation (7).…”

Section: Discussionmentioning

confidence: 99%

“…The Th1 cytokine IFN-g activates NO production in macrophages, which subsequently enhances mycobactericidal activities (2). IL-12 acts as a linker of innate and acquired immunities by inducing Th1 cell differentiation, releasing IFN-g from Th1 cells, and activating macrophages (2,3). Both cytokines are involved in protection against MAC infection because patients with defects in IFN-g/IL-12 signaling are more susceptible to disseminated and extrapulmonary MAC diseases (4,5).…”

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confidence: 99%

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Role of Th1/Th17 Balance Regulated by T-bet in a Mouse Model of Mycobacterium avium Complex Disease

Matsuyama

Ishii

Yageta

et al. 2014

The Journal of Immunology

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Th1 immune responses are thought to be important in protection against intracellular pathogens. T-bet is a critical regulator for Th1 cell differentiation and Th1 cytokine production. The aim of this study was to determine the role of T-bet in host defense against Mycobacterium avium complex (MAC) infection. Wild-type mice, T-bet–deficient mice, and T-bet–overexpressing mice were infected with MAC via intratracheal inoculation. Macrophages and dendritic cells obtained from these mice were incubated with MAC. T-bet–deficient mice were highly susceptible to MAC, compared with wild-type mice and T-bet–overexpressing mice. Neutrophilic pulmonary inflammation was also enhanced in T-bet–deficient mice, but attenuated in T-bet–overexpressing mice, following MAC infection. Cytokine expression shifted toward Th1 in the lung and spleen of T-bet–overexpressing mice, but toward Th17 in T-bet–deficient mice. IFN-γ supplementation to T-bet–deficient mice reduced systemic MAC growth but did not reduce pulmonary inflammation. In contrast, neutralization of IL-17 in T-bet–deficient mice reduced pulmonary inflammation but did not affect mycobacterial growth in any organs tested. T-bet–deficient T cells tended to differentiate toward Th17 cells in vitro following exposure to MAC. Treatment with NO donor suppressed MAC-induced Th17 cell differentiation of T-bet–deficient T cells. This study identified that the fine balance between Th1 and Th17 responses is essential in defining the outcome of MAC disease. T-bet functions as a regulator for Th1/Th17 balance and is a critical determinant for host resistance to MAC infection by controlling cytokine and NO levels.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Role of Th1/Th17 Balance Regulated by T-bet in a Mouse Model of Mycobacterium avium Complex Disease

Matsuyama

Ishii

Yageta

et al. 2014

The Journal of Immunology

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“…IL-12 is composed of the subunits p35/p40, IL-23 of p19/p40, IL-27 of p28/Ebi3, and IL-35 of p35/Ebi3 with expression of the distinct subunits being regulated independently (166). In addition, IL-12p40 can also be secreted both as a homodimer (IL-12p80 or IL-12p(40) 2 ) and as a monomer (IL-12p40) (167). Both macrophages and dendritic cells are major producers of IL-12p40, IL-12, IL-23 and IL-27 (168).…”

Section: Cytokinesmentioning

confidence: 99%

Cytokines and Chemokines inMycobacterium tuberculosisInfection

et al. 2016

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Chemokines and cytokines are critical for initiating and coordinating the organized and sequential recruitment and activation of cells into Mycobacterium tuberculosis -infected lungs. Correct mononuclear cellular recruitment and localization are essential to ensure control of bacterial growth without the development of diffuse and damaging granulocytic inflammation. An important block to our understanding of TB pathogenesis lies in dissecting the critical aspects of the cytokine/chemokine interplay in light of the conditional role these molecules play throughout infection and disease development. Much of the data highlighted in this review appears at first glance to be contradictory, but it is the balance between the cytokines and chemokines that is critical, and the “goldilocks” (not too much and not too little) phenomenon is paramount in any discussion of the role of these molecules in TB. Determination of how the key chemokines/cytokines and their receptors are balanced and how the loss of that balance can promote disease is vital to understanding TB pathogenesis and to identifying novel therapies for effective eradication of this disease.

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“…The influence of IL-12 on CD8+ T cell differentiation has also been demonstrated through its action as the third signal (66). In addition, this cytokine acts on B cells, favoring IgG2a class switching and inhibiting IgE and IgG1 (67). A recombinant BCG containing a fusion of the IL-12p70 and ESAT-6 genes was shown to induce higher IFN-γ production than the other BCG constructs analyzed (BCG, rBCG-ESAT-6, and rBCG-IL-12), as well as higher total IgG, IgG1, and IgG2a levels.…”

Section: Cytokine Fusion With Mtb Proteins and Live Recombinant Vectomentioning

confidence: 99%

Role of Fused Mycobacterium tuberculosis Immunogens and Adjuvants in Modern Tuberculosis Vaccines

2014

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Several approaches have been developed to improve or replace the only available vaccine for tuberculosis (TB), BCG (Bacille Calmette Guerin). The development of subunit protein vaccines is a promising strategy because it combines specificity and safety. In addition, subunit protein vaccines can be designed to have selected immune epitopes associated with immunomodulating components to drive the appropriate immune response. However, the limited antigens present in subunit vaccines reduce their capacity to stimulate a complete immune response compared with vaccines composed of live attenuated or killed microorganisms. This deficiency can be compensated by the incorporation of adjuvants in the vaccine formulation. The fusion of adjuvants with Mycobacterium tuberculosis (Mtb) proteins or immune epitopes has the potential to become the new frontier in the TB vaccine development field. Researchers have addressed this approach by fusing the immune epitopes of their vaccines with molecules such as interleukins, lipids, lipoproteins, and immune stimulatory peptides, which have the potential to enhance the immune response. The fused molecules are being tested as subunit vaccines alone or within live attenuated vector contexts. Therefore, the objectives of this review are to discuss the association of Mtb fusion proteins with adjuvants; Mtb immunogens fused with adjuvants; and cytokine fusion with Mtb proteins and live recombinant vectors expressing cytokines. The incorporation of adjuvant molecules in a vaccine can be complex, and developing a stable fusion with proteins is a challenging task. Overall, the fusion of adjuvants with Mtb epitopes, despite the limited number of studies, is a promising field in vaccine development.

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Role of interleukin-12 family cytokines in the cellular response to mycobacterial disease

Cited by 59 publications

References 93 publications

Role of Th1/Th17 Balance Regulated by T-bet in a Mouse Model of Mycobacterium avium Complex Disease

Role of Th1/Th17 Balance Regulated by T-bet in a Mouse Model of Mycobacterium avium Complex Disease

Cytokines and Chemokines inMycobacterium tuberculosisInfection

Role of Fused Mycobacterium tuberculosis Immunogens and Adjuvants in Modern Tuberculosis Vaccines

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