Mechanisms of Immune Modulation by Fasciola Hepatica: The Impact of Innate Immune Cells on the Developing Adaptive Immune Response

Intracellular phagosomal pathogens represent a formidable challenge for innate immune cells, as, paradoxically, these phagocytic cells can act as both host cells that support pathogen replication and, when properly activated, are the critical cells that mediate pathogen elimination. Infection by parasites of the Leishmania genus provides an excellent model organism to investigate this complex host-pathogen interaction. In this review we focus on the dynamics of Leishmania amazonensis infection and the host innate immune response, including the impact of the adaptive immune response on phagocytic host cell recruitment and activation. L. amazonensis infection represents an important public health problem in South America where, distinct from other Leishmania parasites, it has been associated with all three clinical forms of leishmaniasis in humans: cutaneous, muco-cutaneous and visceral. Experimental observations demonstrate that most experimental mouse strains are susceptible to L. amazonensis infection, including the C57BL/6 mouse, which is resistant to other species such as Leishmania major, Leishmania braziliensis and Leishmania infantum. In general, the CD4+ T helper (Th)1/Th2 paradigm does not sufficiently explain the progressive chronic disease established by L. amazonensis, as strong cell-mediated Th1 immunity, or a lack of Th2 immunity, does not provide protection as would be predicted. Recent findings in which the balance between Th1/Th2 immunity was found to influence permissive host cell availability via recruitment of inflammatory monocytes has also added to the complexity of the Th1/Th2 paradigm. In this review we discuss the roles played by innate cells starting from parasite recognition through to priming of the adaptive immune response. We highlight the relative importance of neutrophils, monocytes, dendritic cells and resident macrophages for the establishment and progressive nature of disease following L. amazonensis infection.

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Innate Immune Cells and Their Contribution to T-Cell-Based Immunotherapy

International Journal of Molecular Sciences ◽

10.3390/ijms21124441 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4441 ◽

Cited By ~ 1

Author(s):

Pierpaolo Ginefra ◽

Girieca Lorusso ◽

Nicola Vannini

Keyword(s):

T Cells ◽

T Cell ◽

Cancer Immunotherapy ◽

Cancer Patients ◽

Immune Cells ◽

Adoptive Cell Therapy ◽

Adaptive Immune Response ◽

Immune Checkpoint Blockade ◽

Innate Immune ◽

Innate Immune Cells

In recent years, immunotherapy has become the most promising therapy for a variety of cancer types. The development of immune checkpoint blockade (ICB) therapies, the adoptive transfer of tumor-specific T cells (adoptive cell therapy (ACT)) or the generation of T cells engineered with chimeric antigen receptors (CAR) have been successfully applied to elicit durable immunological responses in cancer patients. However, not all the patients respond to these therapies, leaving a consistent gap of therapeutic improvement that still needs to be filled. The innate immune components of the tumor microenvironment play a pivotal role in the activation and modulation of the adaptive immune response against the tumor. Indeed, several efforts are made to develop strategies aimed to harness innate immune cells in the context of cancer immunotherapy. In this review, we describe the contribution of innate immune cells in T-cell-based cancer immunotherapy and the therapeutic approaches implemented to broaden the efficacy of these therapies in cancer patients.

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Rapid Weight Loss, Central Obesity Improvement and Blood Glucose Reduction Are Associated with a Stronger Adaptive Immune Response Following COVID-19 mRNA Vaccine

Vaccines ◽

10.3390/vaccines10010079 ◽

2022 ◽

Vol 10 (1) ◽

pp. 79

Author(s):

Mikiko Watanabe ◽

Angela Balena ◽

Davide Masi ◽

Rossella Tozzi ◽

Renata Risi ◽

...

Keyword(s):

Immune Response ◽

Weight Loss ◽

Blood Glucose ◽

Adaptive Immune Response ◽

Humoral Response ◽

Rapid Weight Loss ◽

Low Carbohydrate Diet ◽

Adaptive Immune ◽

Glucose Reduction ◽

The Impact

Obesity is associated with a poor COVID-19 prognosis, and it seems associated with reduced humoral response to vaccination. Public health campaigns have advocated for weight loss in subjects with obesity, hoping to eliminate this risk. However, no evidence proves that weight loss leads to a better prognosis or a stronger immune response to vaccination. We aimed to investigate the impact of rapid weight loss on the adaptive immune response in subjects with morbid obesity. Twenty-one patients followed a hypocaloric, very-low-carbohydrate diet one week before to one week after the two mRNA vaccine doses. The diet’s safety and efficacy were assessed, and the adaptive humoral (anti-SARS CoV-2 S antibodies, Abs) and cell-mediated responses (IFNγ secretion on stimulation with two different SARS CoV-2 peptide mixes, IFNγ-1 and IFNγ-2) were evaluated. The patients lost ~10% of their body weight with metabolic improvement. A high baseline BMI correlated with a poor immune response (R −0.558, p = 0.013 for IFNγ-1; R −0.581, p = 0.009 for IFNγ-2; R −0.512, p = 0.018 for Abs). Furthermore, there was a correlation between weight loss and higher IFNγ-2 (R 0.471, p = 0.042), and between blood glucose reduction and higher IFNγ-1 (R 0.534, p = 0.019), maintained after weight loss and waist circumference reduction adjustment. Urate reduction correlated with higher Abs (R 0.552, p = 0.033). In conclusion, obesity is associated with a reduced adaptive response to a COVID-19 mRNA vaccine, and weight loss and metabolic improvement may reverse the effect.

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Adipocytes, Innate Immunity and Obesity: A Mini-Review

Frontiers in Immunology ◽

10.3389/fimmu.2021.650768 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alecia M. Blaszczak ◽

Anahita Jalilvand ◽

Willa A. Hsueh

Keyword(s):

Adipose Tissue ◽

Immune System ◽

Immune Cells ◽

Adaptive Immune System ◽

Innate Immune ◽

Lymphoid Cells ◽

Innate Immune Cells ◽

Adaptive Immune

The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.

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Helminth Infections: Recognition and Modulation of the Immune Response by Innate Immune Cells

Frontiers in Immunology ◽

10.3389/fimmu.2018.00664 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 34

Author(s):

Claudia Cristina Motran ◽

Leonardo Silvane ◽

Laura Silvina Chiapello ◽

Martin Gustavo Theumer ◽

Laura Fernanda Ambrosio ◽

...

Keyword(s):

Immune Response ◽

Immune Cells ◽

Innate Immune ◽

Innate Immune Cells ◽

Helminth Infections

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Salmonella escapes adaptive immune response via SIRT2 mediated modulation of innate immune response in dendritic cells

PLoS Pathogens ◽

10.1371/journal.ppat.1007437 ◽

2018 ◽

Vol 14 (11) ◽

pp. e1007437 ◽

Cited By ~ 7

Author(s):

Mayuri Gogoi ◽

Kasturi Chandra ◽

Mohsen Sarikhani ◽

Ramya Ramani ◽

Nagalingam Ravi Sundaresan ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Innate Immune Response ◽

Adaptive Immune Response ◽

Innate Immune ◽

Adaptive Immune

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RNA N6-Methyladenosine Modifications and the Immune Response

Journal of Immunology Research ◽

10.1155/2020/6327614 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Ya-Nan Wang ◽

Chen-Yang Yu ◽

Hong-Zhong Jin

Keyword(s):

Immune Response ◽

Biological Effects ◽

Biological Significance ◽

Adaptive Immune Response ◽

Noncoding Rnas ◽

Innate Immune ◽

Messenger Rnas ◽

Adaptive Immune ◽

Wide Range ◽

Higher Eukaryotes

N6-methyladenosine (m6A) is the most important modification of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) in higher eukaryotes. Modulation of m6A modifications relies on methyltransferases and demethylases. The discovery of binding proteins confirms that the m6A modification has a wide range of biological effects and significance at the molecular, cellular, and physiological levels. In recent years, techniques for investigating m6A modifications of RNA have developed rapidly. This article reviews the biological significance of RNA m6A modifications in the innate immune response, adaptive immune response, and viral infection.

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Changes in immune responses to oxidized LDL epitopes during aging in hypercholesterolemic apoE(−/−) mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00511.2005 ◽

2006 ◽

Vol 291 (6) ◽

pp. R1644-R1650 ◽

Cited By ~ 4

Author(s):

Paul C. Dimayuga ◽

Xiaoning Zhao ◽

Juliana Yano ◽

Kuang-Yuh Chyu

Keyword(s):

Immune Response ◽

Immune Responses ◽

Time Course ◽

Oxidized Ldl ◽

Adaptive Immune Response ◽

Adaptive Immune System ◽

Innate Immune ◽

Collagen Content ◽

Aortic Sinus ◽

Adaptive Immune

Atherosclerosis is a disease associated with aging and is subject to modulation by both the innate and adaptive immune system. The time course of age-dependent changes in immune regulation in the context of atherosclerosis has not been characterized. This study aims to describe alteration of the immune responses to oxidized LDL (oxLDL) during aging that is associated with changes in plaque size and phenotype in apoE(−/−) mice. Mice fed a Western diet were euthanized at 15–17, 36, or >52 wk of age. The descending aortas were stained for assessment of extent of atherosclerosis. Plaque lipid, macrophage, and collagen content were evaluated in aortic sinus lesions. The adaptive immune response to oxLDL was assessed using anti-malondialdehyde-oxidized LDL (MDA-LDL) and copper-oxidized LDL (Cu-oxLDL) IgG, and the innate immune response was assessed using anti-Cu-oxLDL and phosphorylcholine (PC) IgM. Aging was associated with a significant increase in plaque area and collagen content and a decrease in plaque macrophage and lipid content. MDA-LDL IgG significantly increased at 36 wk but was reduced in mice >52 wk. Cu-oxLDL IgG increased with age and IgG-apoB immune complexes were increased in the >52 wk group. Cu-oxLDL and PC IgM significantly increased with age. The expression of splenic cytokines such as IFN-γ, IL-4, and IL-10 increased with age. Our study shows a generalized increase in innate immune responses associated with progression of atherosclerosis and a less inflammatory and less lipid-containing plaque phenotype during aging. The adaptive immune response appeared to be less generalized, with a specific reduction in MDA-LDL IgG.

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