Interleukin-12 and tuberculosis: an old story revisited

Cooper, Andrea M.; Solache, Alejandra; Khader, Shabaana A.

doi:10.1016/j.coi.2007.07.004

Cited by 132 publications

(103 citation statements)

References 48 publications

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“…IFN-deficiency has been considered to be a major factor in the etiopathogenesis for MAC infections [27]. IL-12 plays an important role in defense against mycobacterial infections by inducing production of IFN-, which then binds to IFN-R on macrophages to activate them to eliminate mycobacterial [28][29][30]. Our patients also had impaired IFN-production and most severe reduction was observed in the patient # 1 with disseminated MAC infection.…”

Section: Discussionmentioning

confidence: 70%

Selective IgM Deficiency with T Cell Defects and Mycobacterium Avium Complex (MAC) Infection

Gupta¹

2012

TOIJ

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Primary selective IgM deficiency in adults is associated with normal T cell function, and patients clinically manifest with recurrent pyogenic bacterial infections. In this study, we present three patients with selective IgM deficiency with significant defects in T cells and NK cell cytotoxicity, and Mycobacterial avium intracellulare (MAC) infection. T cell defect is characterized by markedly reduced numbers of T cells and T cell subsets, decreased T cell proliferative responses to mitogens and antigens, including PPD, and significantly decreased production of IFN-; however, expression of IFN-receptors is normal. We propose that selective IgM deficiency with significant T cell functional defects might represent a distinct clinical entity, which is associated with increased susceptibility to MAC infection.

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Section: Discussionmentioning

confidence: 70%

Selective IgM Deficiency with T Cell Defects and Mycobacterium Avium Complex (MAC) Infection

Gupta¹

2012

TOIJ

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“…IL-12 activates CD4 + T cells to produce IFN-g (3), and IFN-g-activated Mfs produce NO to kill M. tuberculosis (38). IL-12 plays a critical role in host defenses against M. tuberculosis in mice and humans (44), with Il12b 2/2 mice showing increased susceptibility to M. tuberculosis (45). Severe mycobacterial infections were reported in IL-12R-deficient patients and their cells were deficient in IL-12R signaling and IFN-g production (46).…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxin 1 Contributes to Host Defenses against Mycobacterium tuberculosis

Matsumura

Iwai

Kato-Miyazawa

et al. 2016

The Journal of Immunology

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Peroxiredoxin (PRDX)1 is an antioxidant that detoxifies hydrogen peroxide and peroxinitrite. Compared with wild-type (WT) mice, Prdx1-deficient (Prdx1−/−) mice showed increased susceptibility to Mycobacterium tuberculosis and lower levels of IFN-γ and IFN-γ–producing CD4+ T cells in the lungs after M. tuberculosis infection. IL-12 production, c-Rel induction, and p38 MAPK activation levels were lower in Prdx1−/− than in WT bone marrow–derived macrophages (BMDMs). IFN-γ–activated Prdx1−/− BMDMs did not kill M. tubercuosis effectively. NO production levels were lower, and arginase activity and arginase 1 (Arg1) expression levels were higher, in IFN-γ–activated Prdx1−/− than in WT BMDMs after M. tuberculosis infection. An arginase inhibitor, Nω-hydroxy-nor-arginine, restored antimicrobial activity and NO production in IFN-γ–activated Prdx1−/− BMDMs after M. tuberculosis infection. These results suggest that PRDX1 contributes to host defenses against M. tuberculosis. PRDX1 positively regulates IL-12 production by inducing c-Rel and activating p38 MAPK, and it positively regulates NO production by suppressing Arg1 expression in macrophages infected with M. tuberculosis.

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“…Однако на покоящихся Т-лимфоцитах рецептор к IL-12р70 конституци-онно представлен только одной субъединицей (β1), что снижает его сродство к стимулирующим сигналам IL-12р70. Цитокином, индуцирую-щим экспрессию IL-12Rβ2-субъединицы рецеп-тора к IL-12 на Т-лимфоцитах, является IL-27 [4,7,12,13,24]. IL-27, как и IL-12р70, состоит из двух субъединиц (EBI3 и IL-27p28) и является лигандом для WSX-1/gp130-рецептора Т-клеток.…”

Section: ключевые слова: интерлейкины Il-12 Il-27 рецепторы к интеunclassified

“…зить продукцию IL-2 активированными Th1-кле-тами на поздних стадиях воспалительного про-цесса, контролируя баланс между активацией клеточного иммунного ответа и объемом разру-шения собственных тканей организма; активиро-вать IL-10-секреторную активность регуляторных Т-лимфоцитов (Treg); влиять на макрофагальные клетки, изменяя их бактерицидную активность [13,16,18,22,23,24,26]. Так, показано, что нейтрализа-ция эффектов IL-27 в присутствии IL-12р70 умень-шала численность жизнеспособных M. tuberculosis, извлеченных из макрофагов, а сам IL-27, полу-ченный из макрофагов во время инфекции, на-против, препятствовал контролю за ростом мико-бактериальной популяции [18].…”

Section: т 16 №unclassified

Secretion of Il-12, Il-27 by Mononuclear Leukocytes and Expression of Their Receptors on T-Lymphocytes in Conditions of Directed Cell Induction in Vitro in Pulmonary Tuberculosis

Есимова¹,

Уразова²,

Новицкий³

et al. 2014

Med.Imm.Rus

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Адрес для переписки:Есимова Ирина Евгеньевна к.м.н., докторант кафедры патофизиологии ГБОУ ВПО «Сибирский государственный медицинский университет» 634009, Россия, г. Томск, пр. Ленина, 229, кв. 80. Тел.: 8 (906) 199-15-73. E-mail: orevi@mail Ключевые слова: интерлейкины, рецепторы к интерлейкинам, туберкулез легких 238 Оригинальные статьиOriginal articles Медицинская иммунология 2014, Т. 16, № 3, стр. 237-246 © 2014, СПб РО РААКИ Medical Immunology 2014, Vol. 16, 3, pp. 237-246 © 2014 SECRETION OF IL-12, IL-27 BY MONONUCLEAR LEUKOCYTES AND EXPRESSION OF THEIR RECEPTORS ON T-LYMPHOCYTES IN CONDITIONS OF DIRECTED CELL INDUCTION IN VITRO IN PULMONARY TUBERCULOSISEsimova I.E., Urazova O.I., Novitskiy V.V., Khasanova R.R., Filinyuk O.V. Siberian State Medical University, Tomsk, Russian FederationAbstract. The article presents the results of studies concerning secretion of cytokines belonging to interleukin 12 family, i.e., IL-12р70, IL-12р40, IL-12р35 and IL-27 in mononuclear blood leukocytes, as well as expression of their specific receptors on T-lymphocytes from tuberculosis patients under the in vitro conditions of directed (resp., antigen-and cytokine-mediated) cell induction. In patients with pulmonary TB, we have registered suppression of both spontaneous and BCG-induced secretion of IL-12р70 and IL-12р35, along with overproduction of IL-12р40 and IL-27. Furthermore, a decrease in relative contents of СD3 . It was shown that the detectable changes are unidirectional in most cases, being dependent on clinical form of the disease and sensitivity of the etiological agent to anti-tuberculosis drugs.

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Interleukin-12 and tuberculosis: an old story revisited

Cited by 132 publications

References 48 publications

Selective IgM Deficiency with T Cell Defects and Mycobacterium Avium Complex (MAC) Infection

Selective IgM Deficiency with T Cell Defects and Mycobacterium Avium Complex (MAC) Infection

Peroxiredoxin 1 Contributes to Host Defenses against Mycobacterium tuberculosis

Secretion of Il-12, Il-27 by Mononuclear Leukocytes and Expression of Their Receptors on T-Lymphocytes in Conditions of Directed Cell Induction in Vitro in Pulmonary Tuberculosis

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