scholarly journals Differential and sequential immunomodulatory role of neutrophils and Ly6Chi inflammatory monocytes during antiviral antibody therapy

2021 ◽  
pp. 1-56
Author(s):  
Jennifer Lambour ◽  
Maria Naranjo-Gomez ◽  
Myriam Boyer-Clavel ◽  
Mireia Pelegrin
Keyword(s):  
Antibody Therapy ◽  
Inflammatory Monocytes ◽  
Antiviral Antibody

scholarly journals Differential and sequential immunomodulatory role of neutrophils and Ly6Chi inflammatory monocytes during antiviral antibody therapy

2020 ◽  
Author(s):  
Jennifer Lambour ◽  
Mar Naranjo-Gomez ◽  
Myriam Boyer-Clavel ◽  
Mireia Pelegrin
Keyword(s):  
Immune Responses ◽  
Antibody Therapy ◽  
Myeloid Cell ◽  
Cell Types ◽  
Retroviral Infection ◽  
Antiviral Immune Response ◽  
Inflammatory Monocytes ◽  
Cytokines And Chemokines

AbstractAntiviral monoclonal antibodies (mAbs) can generate protective immunity through Fc-Fcγ Rs interactions. Using a mouse model of retroviral infection, we previously showed a crucial role for immune complexes (ICs) in the enhancement of T-cell responses through FcγR-mediated activation of dendritic cells (DCs). However, IC-FcγR interactions involve different cells of the immune system other than DCs such as neutrophils and monocytes. These two myeloid cell-types are innate effector cells rapidly recruited to sites of infection. In addition to being key cells to fight against invading pathogens, they are also endowed with immunomodulatory properties. While the role of DCs in enhancing antiviral immune responses upon mAb treatment has been addressed in several studies, the role of neutrophils and monocytes has been much less studied. Here we addressed how mAb therapy affects the functional activation of neutrophils and inflammatory monocytes in retrovirus-infected mice. We found that both cell-types activated in vitro by viral ICs secreted high levels of chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced FcγRIV upregulation. Similarly, infection and mAb-treatment upregulated FcγRIV expression on neutrophils and inflammatory monocytes and enhanced their cytokines and chemokines secretion. Notably, upon antibody therapy neutrophils and inflammatory monocytes displayed distinct functional activation states and sequentially modulated the antiviral immune response through the secretion of Th1-type polarizing cytokines and chemokines. Our work provides novel findings on the immunomodulatory role of neutrophils and monocytes in the enhancement of immune responses upon antiviral mAb therapy.

scholarly journals Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321731
Author(s):  
Dominik Aschenbrenner ◽  
Maria Quaranta ◽  
Soumya Banerjee ◽  
Nicholas Ilott ◽  
Joanneke Jansen ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Personalised Medicine ◽  
Mononuclear Phagocytes ◽  
Cytokine Network ◽  
Peripheral Blood Mononuclear ◽  
Transcriptional Signature ◽  
Inflammatory Monocytes ◽  
Transcriptomic Signature ◽  
Inflammatory Bowel

ObjectiveDysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine.DesignWe performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples.ResultsWe characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease.ConclusionOur work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn’s disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23.

scholarly journals CCL2: An Important Mediator Between Tumor Cells and Host Cells in Tumor Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiakang Jin ◽  
Jinti Lin ◽  
Ankai Xu ◽  
Jianan Lou ◽  
Chao Qian ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cell Types ◽  
Host Cells ◽  
Specific Cell ◽  
Tumor Patients ◽  
Multiple Tumor ◽  
Inflammatory Monocytes ◽  
Immunosuppressive Cell ◽  
Tumor Types

Tumor microenvironment (TME) formation is a major cause of immunosuppression. The TME consists of a considerable number of macrophages and stromal cells that have been identified in multiple tumor types. CCL2 is the strongest chemoattractant involved in macrophage recruitment and a powerful initiator of inflammation. Evidence indicates that CCL2 can attract other host cells in the TME and direct their differentiation in cooperation with other cytokines. Overall, CCL2 has an unfavorable effect on prognosis in tumor patients because of the accumulation of immunosuppressive cell subtypes. However, there is also evidence demonstrating that CCL2 enhances the anti-tumor capability of specific cell types such as inflammatory monocytes and neutrophils. The inflammation state of the tumor seems to have a bi-lateral role in tumor progression. Here, we review works focusing on the interactions between cancer cells and host cells, and on the biological role of CCL2 in these processes.

Abstract 2704: A role of the ADCC in the antibody therapy for gastrointestinal carcinoma

2011 ◽  
Author(s):  
Tatsuzo Matsuyama ◽  
Satoshi Kokura ◽  
Tsuguhiro Matsumoto ◽  
Manabu Okajima ◽  
Manabu Okajima ◽  
...  
Keyword(s):  
Antibody Therapy ◽  
Gastrointestinal Carcinoma

scholarly journals Immunosenescence: a key player in cancer development

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Jingyao Lian ◽  
Ying Yue ◽  
Weina Yu ◽  
Yi Zhang
Keyword(s):  
T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Malignant Tumors ◽  
Killer Cell ◽  
Antibody Therapy ◽  
The Elderly ◽  
Mtor Inhibition ◽  
Interleukin 7 ◽  
The Many

Abstract Immunosenescence is a process of immune dysfunction that occurs with age and includes remodeling of lymphoid organs, leading to changes in the immune function of the elderly, which is closely related to the development of infections, autoimmune diseases, and malignant tumors. T cell–output decline is an important feature of immunosenescence as well as the production of senescence-associated secretory phenotype, increased glycolysis, and reactive oxygen species. Senescent T cells exhibit abnormal phenotypes, including downregulation of CD27, CD28, and upregulation of CD57, killer cell lectin-like receptor subfamily G, Tim-3, Tight, and cytotoxic T-lymphocyte-associated protein 4, which are tightly related to malignant tumors. The role of immunosenescence in tumors is sophisticated: the many factors involved include cAMP, glucose competition, and oncogenic stress in the tumor microenvironment, which can induce the senescence of T cells, macrophages, natural killer cells, and dendritic cells. Accordingly, these senescent immune cells could also affect tumor progression. In addition, the effect of immunosenescence on the response to immune checkpoint blocking antibody therapy so far is ambiguous due to the low participation of elderly cancer patients in clinical trials. Furthermore, many other senescence-related interventions could be possible with genetic and pharmacological methods, including mTOR inhibition, interleukin-7 recombination, and NAD+ activation. Overall, this review aims to highlight the characteristics of immunosenescence and its impact on malignant tumors and immunotherapy, especially the future directions of tumor treatment through senescence-focused strategies.

scholarly journals Role of interferon-γand inflammatory monocytes in driving colonic inflammation during acuteClostridium difficileinfection in mice

Immunology ◽  
2017 ◽  
Vol 150 (4) ◽  
pp. 468-477 ◽  
Author(s):  
Andrew J. McDermott ◽  
Nicole R. Falkowski ◽  
Roderick A. McDonald ◽  
Charles R. Frank ◽  
Chinmay R. Pandit ◽  
...  
Keyword(s):  
Colonic Inflammation ◽  
Inflammatory Monocytes

scholarly journals Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Lisa E. Gralinski ◽  
Timothy P. Sheahan ◽  
Thomas E. Morrison ◽  
Vineet D. Menachery ◽  
Kara Jensen ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Host Defense ◽  
Complement System ◽  
Complement Activation ◽  
Fungal Infections ◽  
Central Component ◽  
Lung Pathology ◽  
Inflammatory Monocytes ◽  
The Complement System

ABSTRACT Acute respiratory distress syndrome (ARDS) is immune-driven pathologies that are observed in severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. SARS-CoV emerged in 2002 to 2003 and led to a global outbreak of SARS. As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Using this model, we investigated the role of the complement system during SARS-CoV infection. We observed activation of the complement cascade in the lung as early as day 1 following SARS-CoV infection. To test whether this activation contributed to protective or pathologic outcomes, we utilized mice deficient in C3 (C3–/–), the central component of the complement system. Relative to C57BL/6J control mice, SARS-CoV-infected C3–/– mice exhibited significantly less weight loss and less respiratory dysfunction despite equivalent viral loads in the lung. Significantly fewer neutrophils and inflammatory monocytes were present in the lungs of C3–/– mice than in C56BL/6J controls, and subsequent studies revealed reduced lung pathology and lower cytokine and chemokine levels in both the lungs and the sera of C3–/– mice than in controls. These studies identify the complement system as an important host mediator of SARS-CoV-induced disease and suggest that complement activation regulates a systemic proinflammatory response to SARS-CoV infection. Furthermore, these data suggest that SARS-CoV-mediated disease is largely immune driven and that inhibiting complement signaling after SARS-CoV infection might function as an effective immune therapeutic. IMPORTANCE The complement system is a critical part of host defense to many bacterial, viral, and fungal infections. It works alongside pattern recognition receptors to stimulate host defense systems in advance of activation of the adaptive immune response. In this study, we directly test the role of complement in SARS-CoV pathogenesis using a mouse model and show that respiratory disease is significantly reduced in the absence of complement even though viral load is unchanged. Complement-deficient mice have reduced neutrophilia in their lungs and reduced systemic inflammation, consistent with the observation that SARS-CoV pathogenesis is an immune-driven disease. These data suggest that inhibition of complement signaling might be an effective treatment option following coronavirus infection.

scholarly journals CD4+ but not CD8+ cells are essential for allorejection.

1996 ◽  
Vol 184 (5) ◽  
pp. 2013-2018 ◽  
Author(s):  
N R Krieger ◽  
D P Yin ◽  
C G Fathman
Keyword(s):  
Cd8 T Cells ◽  
Knockout Mice ◽  
Antibody Therapy ◽  
Major Histocompatibility ◽  
Cd4 Cells ◽  
Cd8 Cells ◽  
Targeted Gene Disruption ◽  
Histocompatibility Complex ◽  
Skin Allografts

The generation of knockout mice with targeted gene disruption has provided a valuable tool for studying the immune response. Here we describe the use of CD4 and CD8 knockout mice to examine the role of CD4+ and CD8+ cells in initiating allotransplantation rejection. Pretreatment with a brief course of depletive anti-CD4 monoclonal antibody therapy allowed permanent survival of heart, but not skin, allografts transplanted across a major histocompatibility barrier. However, skin as well as heart grafts were permanently accepted in the CD4 knockout mice. Transfer of CD4+ cells into CD4 knockout recipient mice 1 d before skin engraftment reconstituted rejection, demonstrating that CD4+ cells are necessary for initiating rejection of allogeneic transplants. Major histocompatibility complex disparate heart and skin allografts transplanted into CD8 knockout recipients were rejected within 10 d. This study demonstrates that CD4+ but not CD8+ T cells are absolutely required to initiate allograft rejection.

Sign in / Sign up

Export Citation Format

Share Document