Trypanosoma brucei Invariant Surface Glycoprotein 75 Is an Immunoglobulin Fc Receptor Inhibiting Complement Activation and Antibody-Mediated Cellular Phagocytosis
J Immunol. 2024 Feb 23:ji2300862. doi: 10.4049/jimmunol.2300862. Online ahead of print.ABSTRACTVarious subspecies of the unicellular parasite Trypanosoma brucei cause sleeping sickness, a neglected tropical disease affecting millions of individuals and domestic animals. Immune evasion mechanisms play a pivotal role in parasite survival within the host and enable the parasite to establish a chronic infection. In particular, the rapid switching of variant surface glycoproteins covering a large proportion of the parasite's surface enables the parasite to avoid clearance by the adaptive immune system of the host. In this artic...
Source: Journal of Immunology - February 23, 2024 Category: Allergy & Immunology Authors: Jakob Hauge Mikkelsen Kristian St ødkilde Maria Paulad òttir Jensen Annette Gudmann Hansen Qi Wu Josefine Lorentzen Jonas Heilskov Graversen Gregers Rom Andersen Robert Andrew Fenton Anders Etzerodt Steffen Thiel Christian Brix Folsted Andersen Source Type: research

IDO1 Inhibition Promotes Activation of Tumor-intrinsic STAT3 Pathway and Induces Adverse Tumor-protective Effects
In this study, we conducted single-cell RNA sequencing to determine the overall response to apo-IDO1 inhibitor administration. Interestingly, although apo-IDO1 inhibitors were found to significantly activate intratumoral immune cells (mouse colon cancer cell CT26 transplanted in BALB/C mice), such as T cells, macrophages, and NK cells, they also stimulated the infiltration of M2 macrophages. Moreover, these inhibitors prompted monocytes and macrophages to secrete elevated levels of IL-6, which in turn activated the JAK2/STAT3 signaling pathway in tumor cells. Consequently, this activation enables tumor cells to survive eve...
Source: Journal of Immunology - February 23, 2024 Category: Allergy & Immunology Authors: Longbo Yu Lingyan Xu Yunjie Chen Yicheng Rong Yi Zou Shushan Ge Tiancong Wu Yisheng Lai Qiang Xu Wenjie Guo Wen Liu Source Type: research

Astaxanthin Inhibits STING Carbonylation and Enhances Antiviral Responses
In this study, we showed that astaxanthin markedly inhibited HSV-1-induced lipid peroxidation and inflammatory responses and enhanced the induction of type I IFN in C57BL/6J mice and mouse primary peritoneal macrophages. Mechanistically, astaxanthin inhibited HSV-1 infection and oxidative stress-induced STING carbonylation and consequently promoted STING translocation to the Golgi apparatus and oligomerization, which activated STING-dependent host defenses. Thus, our study reveals that astaxanthin displays a strong antiviral activity by targeting STING, suggesting that astaxanthin might be a promising STING agonist and a t...
Source: Journal of Immunology - February 23, 2024 Category: Allergy & Immunology Authors: Qizhao Li Mutian Jia Hui Song Jun Peng Wei Zhao Weifang Zhang Source Type: research

Trypanosoma brucei Invariant Surface Glycoprotein 75 Is an Immunoglobulin Fc Receptor Inhibiting Complement Activation and Antibody-Mediated Cellular Phagocytosis
J Immunol. 2024 Feb 23:ji2300862. doi: 10.4049/jimmunol.2300862. Online ahead of print.ABSTRACTVarious subspecies of the unicellular parasite Trypanosoma brucei cause sleeping sickness, a neglected tropical disease affecting millions of individuals and domestic animals. Immune evasion mechanisms play a pivotal role in parasite survival within the host and enable the parasite to establish a chronic infection. In particular, the rapid switching of variant surface glycoproteins covering a large proportion of the parasite's surface enables the parasite to avoid clearance by the adaptive immune system of the host. In this artic...
Source: Journal of Immunology - February 23, 2024 Category: Allergy & Immunology Authors: Jakob Hauge Mikkelsen Kristian St ødkilde Maria Paulad òttir Jensen Annette Gudmann Hansen Qi Wu Josefine Lorentzen Jonas Heilskov Graversen Gregers Rom Andersen Robert Andrew Fenton Anders Etzerodt Steffen Thiel Christian Brix Folsted Andersen Source Type: research

IDO1 Inhibition Promotes Activation of Tumor-intrinsic STAT3 Pathway and Induces Adverse Tumor-protective Effects
In this study, we conducted single-cell RNA sequencing to determine the overall response to apo-IDO1 inhibitor administration. Interestingly, although apo-IDO1 inhibitors were found to significantly activate intratumoral immune cells (mouse colon cancer cell CT26 transplanted in BALB/C mice), such as T cells, macrophages, and NK cells, they also stimulated the infiltration of M2 macrophages. Moreover, these inhibitors prompted monocytes and macrophages to secrete elevated levels of IL-6, which in turn activated the JAK2/STAT3 signaling pathway in tumor cells. Consequently, this activation enables tumor cells to survive eve...
Source: Journal of Immunology - February 23, 2024 Category: Allergy & Immunology Authors: Longbo Yu Lingyan Xu Yunjie Chen Yicheng Rong Yi Zou Shushan Ge Tiancong Wu Yisheng Lai Qiang Xu Wenjie Guo Wen Liu Source Type: research

Astaxanthin Inhibits STING Carbonylation and Enhances Antiviral Responses
In this study, we showed that astaxanthin markedly inhibited HSV-1-induced lipid peroxidation and inflammatory responses and enhanced the induction of type I IFN in C57BL/6J mice and mouse primary peritoneal macrophages. Mechanistically, astaxanthin inhibited HSV-1 infection and oxidative stress-induced STING carbonylation and consequently promoted STING translocation to the Golgi apparatus and oligomerization, which activated STING-dependent host defenses. Thus, our study reveals that astaxanthin displays a strong antiviral activity by targeting STING, suggesting that astaxanthin might be a promising STING agonist and a t...
Source: Journal of Immunology - February 23, 2024 Category: Allergy & Immunology Authors: Qizhao Li Mutian Jia Hui Song Jun Peng Wei Zhao Weifang Zhang Source Type: research

Trypanosoma brucei Invariant Surface Glycoprotein 75 Is an Immunoglobulin Fc Receptor Inhibiting Complement Activation and Antibody-Mediated Cellular Phagocytosis
J Immunol. 2024 Feb 23:ji2300862. doi: 10.4049/jimmunol.2300862. Online ahead of print.ABSTRACTVarious subspecies of the unicellular parasite Trypanosoma brucei cause sleeping sickness, a neglected tropical disease affecting millions of individuals and domestic animals. Immune evasion mechanisms play a pivotal role in parasite survival within the host and enable the parasite to establish a chronic infection. In particular, the rapid switching of variant surface glycoproteins covering a large proportion of the parasite's surface enables the parasite to avoid clearance by the adaptive immune system of the host. In this artic...
Source: Journal of Immunology - February 23, 2024 Category: Allergy & Immunology Authors: Jakob Hauge Mikkelsen Kristian St ødkilde Maria Paulad òttir Jensen Annette Gudmann Hansen Qi Wu Josefine Lorentzen Jonas Heilskov Graversen Gregers Rom Andersen Robert Andrew Fenton Anders Etzerodt Steffen Thiel Christian Brix Folsted Andersen Source Type: research

The Role of Fc Receptors in the Innate Immune System of Flounders Purported to Be Homologs of Fc γRII and FcγRIII
In this study, we prepared rFcγRIII as well as its corresponding Abs to investigate the potential roles of FcγRII and FcγRIII in the Ab-dependent immune response of IgM+ B cells. Our findings indicate that, unlike FcγRII, FcγRIII does not participate in Ab-dependent cellular phagocytosis. Instead, it is involved in cytokine production and bacterial killing in mIgM+ B lymphocytes. Additionally, we identified platelet-derived ADAM17 as a key factor in regulating FcγRIII shedding and cytokine release in mIgM+ B lymphocytes. These results elucidate the functions of FcγRII and FcγRIII in the innate immunology of mIgM+ B...
Source: Journal of Immunology - February 21, 2024 Category: Allergy & Immunology Authors: Yan-Bo Hao Jing Xing Xiu-Zhen Sheng Heng Chi Xiao-Qian Tang Wen-Bin Zhan Source Type: research

Fosl2 Deficiency Predisposes Mice to Osteopetrosis, Leading to Bone Marrow Failure
In this study, we show that Fosl2 maintains hematopoietic stem cell (HSC) quiescence and differentiation while controlling the inflammatory response via macrophages. Fosl2-specific deletion in the hematopoietic system caused the expansion of HSCs and myeloid cell growth while affecting erythroid and B cell differentiation. Fosl2 inactivation enhanced macrophage M1 polarization and stimulated proinflammatory cytokines and myeloid growth factors, skewing HSCs toward myeloid cell differentiation, similar to hematopoietic alterations in arthritic mice. Loss of Fosl2 mediated by Vav-iCre also displays an unexpected deletion in ...
Source: Journal of Immunology - February 21, 2024 Category: Allergy & Immunology Authors: Jinfeng Chen Yi Wen Lili Lin Yuchen Cui Zhenyu Chen Jing Gao Yifang Zhuang Qi Chen Source Type: research

IL-33 Induces Cellular and Exosomal miR-146a Expression as a Feedback Inhibitor of Mast Cell Function
J Immunol. 2024 Feb 21:ji2200916. doi: 10.4049/jimmunol.2200916. Online ahead of print.ABSTRACTIL-33 is an inflammatory cytokine that promotes allergic disease by activating group 2 innate lymphoid cells, Th2 cells, and mast cells. IL-33 is increased in asthmatics, and its blockade suppresses asthma-like inflammation in mouse models. Homeostatic control of IL-33 signaling is poorly understood. Because the IL-33 receptor, ST2, acts via cascades used by the TLR family, similar feedback mechanisms may exist. MicroRNA (miR)-146a is induced by LPS-mediated TLR4 signaling and serves as a feedback inhibitor. Therefore, we explore...
Source: Journal of Immunology - February 21, 2024 Category: Allergy & Immunology Authors: Marcela T Taruselli Amina Abdul Qayum Daniel Abebayehu Heather L Caslin Jordan M Dailey Aditya Kotha Jason R Burchett Sydney A Kee Tania D Maldonado Boyang Ren Wei Chao Lin Zou Tamara T Haque David Straus John J Ryan Source Type: research

The Role of Fc Receptors in the Innate Immune System of Flounders Purported to Be Homologs of Fc γRII and FcγRIII
In this study, we prepared rFcγRIII as well as its corresponding Abs to investigate the potential roles of FcγRII and FcγRIII in the Ab-dependent immune response of IgM+ B cells. Our findings indicate that, unlike FcγRII, FcγRIII does not participate in Ab-dependent cellular phagocytosis. Instead, it is involved in cytokine production and bacterial killing in mIgM+ B lymphocytes. Additionally, we identified platelet-derived ADAM17 as a key factor in regulating FcγRIII shedding and cytokine release in mIgM+ B lymphocytes. These results elucidate the functions of FcγRII and FcγRIII in the innate immunology of mIgM+ B...
Source: Journal of Immunology - February 21, 2024 Category: Allergy & Immunology Authors: Yan-Bo Hao Jing Xing Xiu-Zhen Sheng Heng Chi Xiao-Qian Tang Wen-Bin Zhan Source Type: research

Fosl2 Deficiency Predisposes Mice to Osteopetrosis, Leading to Bone Marrow Failure
In this study, we show that Fosl2 maintains hematopoietic stem cell (HSC) quiescence and differentiation while controlling the inflammatory response via macrophages. Fosl2-specific deletion in the hematopoietic system caused the expansion of HSCs and myeloid cell growth while affecting erythroid and B cell differentiation. Fosl2 inactivation enhanced macrophage M1 polarization and stimulated proinflammatory cytokines and myeloid growth factors, skewing HSCs toward myeloid cell differentiation, similar to hematopoietic alterations in arthritic mice. Loss of Fosl2 mediated by Vav-iCre also displays an unexpected deletion in ...
Source: Journal of Immunology - February 21, 2024 Category: Allergy & Immunology Authors: Jinfeng Chen Yi Wen Lili Lin Yuchen Cui Zhenyu Chen Jing Gao Yifang Zhuang Qi Chen Source Type: research

IL-33 Induces Cellular and Exosomal miR-146a Expression as a Feedback Inhibitor of Mast Cell Function
J Immunol. 2024 Feb 21:ji2200916. doi: 10.4049/jimmunol.2200916. Online ahead of print.ABSTRACTIL-33 is an inflammatory cytokine that promotes allergic disease by activating group 2 innate lymphoid cells, Th2 cells, and mast cells. IL-33 is increased in asthmatics, and its blockade suppresses asthma-like inflammation in mouse models. Homeostatic control of IL-33 signaling is poorly understood. Because the IL-33 receptor, ST2, acts via cascades used by the TLR family, similar feedback mechanisms may exist. MicroRNA (miR)-146a is induced by LPS-mediated TLR4 signaling and serves as a feedback inhibitor. Therefore, we explore...
Source: Journal of Immunology - February 21, 2024 Category: Allergy & Immunology Authors: Marcela T Taruselli Amina Abdul Qayum Daniel Abebayehu Heather L Caslin Jordan M Dailey Aditya Kotha Jason R Burchett Sydney A Kee Tania D Maldonado Boyang Ren Wei Chao Lin Zou Tamara T Haque David Straus John J Ryan Source Type: research

Comment on "Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer-BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines"
J Immunol. 2024 Mar 1;212(5):753. doi: 10.4049/jimmunol.2300425.NO ABSTRACTPMID:38377475 | DOI:10.4049/jimmunol.2300425 (Source: Journal of Immunology)
Source: Journal of Immunology - February 20, 2024 Category: Allergy & Immunology Authors: Abraham Al-Ahmad Source Type: research

TIPE2: A Candidate for Targeting Antitumor Immunotherapy
J Immunol. 2024 Mar 1;212(5):755-763. doi: 10.4049/jimmunol.2300433.ABSTRACTTNF-α-induced protein 8-like 2 (TIPE2 or TNFAIP8L2) is a recently discovered negative regulator of innate and adaptive immunity. TIPE2 is expressed in a wide range of tissues, both immune and nonimmune, and is implicated in the maintenance of immune homeostasis within the immune system. Furthermore, TIPE2 has been shown to play a pivotal role in the regulation of inflammation and the development of tumor. This review focuses on the structural characteristics, expression patterns, and functional roles of TIPE proteins, with a particular emphasis on...
Source: Journal of Immunology - February 20, 2024 Category: Allergy & Immunology Authors: Luxia Xu Feiyan Pan Zhigang Guo Source Type: research