Presence of Infected Gr-1(int)CD11b(hi)CD11c(int) Monocytic Myeloid Derived Suppressor Cells Subverts T Cell Response and Is Associated With Impaired Dendritic Cell Function in Mycobacterium avium-Infected Mice.
Presence of Infected Gr-1(int)CD11b(hi)CD11c(int) Monocytic Myeloid Derived Suppressor Cells Subverts T Cell Response and Is Associated With Impaired Dendritic Cell Function in Mycobacterium avium-Infected Mice.
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DOI：
10.3389/fimmu.2018.02317
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发表时间：
2018
影响因子：
7.3
通讯作者：
Goethe R
中科院分区：
文献类型：
--
作者：
Abdissa K;Nerlich A;Beineke A;Ruangkiattikul N;Pawar V;Heise U;Janze N;Falk C;Bruder D;Schleicher U;Bogdan C;Weiss S;Goethe R
髓源性抑制细胞（MDSC）是具有免疫调节功能的未成熟髓细胞。为了研究MDSC影响抗微生物免疫的机制，我们用两种不同毒力、高毒力的鸟分枝杆菌亚种感染小鼠。禽分枝杆菌25291 （MAA）和低毒力禽分枝杆菌亚种。人犬菌株104 （MAH）。腹腔内感染MAA（而非MAH）可引起严重疾病和单核细胞MDSC （M-MDSC; Gr-1intCD11bhiCD11cint）脾脏大量浸润，表达诱导型NO合成酶（Nos2）并携带大量分枝杆菌。耗尽实验表明M-MDSC对疾病进展至关重要。M-MDSC产生NO影响树突状细胞对抗原的摄取和加工以及CD4+ T细胞的增殖。maa感染缺乏Nos2的小鼠也能诱导M-MDSC。在这些小鼠中，CD4+ T细胞扩增和感染控制得到恢复。然而，T细胞抑制仅部分缓解，表达精氨酸酶（Arg） 1的M-MDSC积累。同样，抑制Arg1也部分挽救了T细胞的增殖。因此，分枝杆菌的毒力导致M-MDSC的诱导，以Nos2-和arg1依赖的方式阻断T细胞反应。
Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with immunomodulatory function. To study the mechanism by which MDSC affect antimicrobial immunity, we infected mice with two M. avium strains of differential virulence, highly virulent Mycobacterium avium subsp. avium strain 25291 (MAA) and low virulent Mycobacterium avium subsp. hominissuis strain 104 (MAH). Intraperitoneal infection with MAA, but not MAH, caused severe disease and massive splenic infiltration of monocytic MDSC (M-MDSC; Gr-1intCD11bhiCD11cint) expressing inducible NO synthase (Nos2) and bearing high numbers of mycobacteria. Depletion experiments demonstrated that M-MDSC were essential for disease progression. NO production by M-MDSC influenced antigen-uptake and processing by dendritic cells and proliferation of CD4+ T cells. M-MDSC were also induced in MAA-infected mice lacking Nos2. In these mice CD4+ T cell expansion and control of infection were restored. However, T cell inhibition was only partially relieved and arginase (Arg) 1-expressing M-MDSC were accumulated. Likewise, inhibition of Arg1 also partially rescued T cell proliferation. Thus, mycobacterial virulence results in the induction of M-MDSC that block the T cell response in a Nos2- and Arg1-dependent manner.
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定义骨髓源性抑制细胞的复杂性和挑战。
影响因子：
3.4
作者：
Damuzzo, Vera;Pinton, Laura;Desantis, Giacomo;Solito, Samantha;Marigo, Ilaria;Bronte, Vincenzo;Mandruzzato, Susanna
通讯作者：
Mandruzzato, Susanna
DOI：
10.1111/j.1749-6632.2012.06607.x
发表时间：
2012-01-01
期刊：
HEMATOPOIETIC STEM CELLS VIII
影响因子：
--
作者：
Bugl, Stefanie;Wirths, Stefan;Kopp, Hans-Georg
通讯作者：
Kopp, Hans-Georg
影响因子：
3.1
作者：
Fulton, SA;Reba, SM;Boom, WH
通讯作者：
Boom, WH
影响因子：
6.4
作者：
Haug, Markus;Awuh, Jane A.;Flo, Trude H.
通讯作者：
Flo, Trude H.
影响因子：
3.1
作者：
Dhama K;Mahendran M;Tiwari R;Dayal Singh S;Kumar D;Singh S;Sawant PM
通讯作者：
Sawant PM