10th Anniversary of Pathogens: T Cells in Pathogenic Infections

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Immunological Responses and Immune Defense Mechanisms".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 17534

Special Issue Editor

Microbial Pathogenesis and Immunology Department, College of Medicine Faculty, Texas A&M University Health Science Center, Bryan, TX, USA
Interests: adaptive immunity; immunotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The year 2022 marks the 10th anniversary of the publication of Pathogens. We would like to express our sincerest thanks to our readers, innumerable authors, anonymous peer reviewers, editors, and all the people working in one way or another for the journal, who have made substantial contributions over the years. We are delighted and proud to celebrate this milestone with a series of Special Issues and events.

To mark this important milestone, a Special Issue entitled “10th Anniversary of Pathogens—T Cells in Pathogenic Infections” will be launched as a part of this celebration.

T cells play a central role in the immune response against pathogenic infections, and T cell-based therapy has shown significant potential as a more powerful approach for treating various pathogenic diseases by harnessing the body's immune system. It is anticipated that responses initiated by immunotherapeutic interventions would explicitly uncover a revenue of discerningly suppressing the individual disease while maintaining the rest of the immune system functionally active. Increasing knowledge in cellular immunology and the host immune response has led to the exciting development of diverse immunotherapeutic modalities, including blockade of immune checkpoints, induction of activation of CD8+ cytotoxic T lymphocytes (CTLs) or CD4+ regulatory T cells (Tregs), the use of non-specific immunosuppressive drugs with associated side effects (e.g., anti-CD3, CD20, or CD52 antibody), adoptive T-cell transfer (ACT)-based therapy, and modulation of local environment, including the tumor microenvironment (TME) and inflammatory microenvironment (IME) to facilitate T cell immunity (e.g., low-dose IL-2 treatment). However, despite enormous advances in the T cell-based therapy, the clinical efficacy and benefits remain less satisfactory due to a variety of factors that lessen antiviral immunity, which include ex vivo T cell production, limited in vivo T cell expansion and persistence, auto antigen identification, generation of antigen-specific T cells, off-target complications, local environment, T cell trafficking to the local sites, etc. Effective strategies for bypassing these barriers should significantly improve T cell-based immunotherapy for pathogenic diseases, and thus are urgently needed.

Prof. Dr. Jianxun Song
Guest Editor

Manuscript Submission Information

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Keywords

  • pathogen
  • T cell
  • immunotherapy
  • persistence
  • cell metabolism
  • immunomodulation
  • exhaustion
  • memory
  • animal model

Published Papers (7 papers)

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Editorial

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2 pages, 176 KiB  
Editorial
T Cells in Pathogenic Infections
Pathogens 2023, 12(4), 578; https://doi.org/10.3390/pathogens12040578 - 10 Apr 2023
Viewed by 878
Abstract
T cells are essential to cell-mediated immunity during bacterial, viral, and fungal infections, and immune-related diseases [...] Full article
(This article belongs to the Special Issue 10th Anniversary of Pathogens: T Cells in Pathogenic Infections)

Research

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12 pages, 749 KiB  
Article
Correlation of Lymphocyte Subpopulations, Clinical Features and Inflammatory Markers during Severe COVID-19 Onset
Pathogens 2023, 12(3), 414; https://doi.org/10.3390/pathogens12030414 - 06 Mar 2023
Cited by 4 | Viewed by 1365
Abstract
Background: Dysregulation of the immune response in the course of COVID-19 has been implicated in critical outcomes. Lymphopenia is evident in severe cases and has been associated with worse outcomes since the early phases of the pandemic. In addition, cytokine storm has been [...] Read more.
Background: Dysregulation of the immune response in the course of COVID-19 has been implicated in critical outcomes. Lymphopenia is evident in severe cases and has been associated with worse outcomes since the early phases of the pandemic. In addition, cytokine storm has been associated with excessive lung injury and concomitant respiratory failure. However, it has also been hypothesized that specific lymphocyte subpopulations (CD4 and CD8 T cells, B cells, and NK cells) may serve as prognostic markers for disease severity. The aim of this study was to investigate possible associations of lymphocyte subpopulations alterations with markers of disease severity and outcomes in patients hospitalized with COVID-19. Materials/Methods: A total of 42 adult hospitalized patients were included in this study, from June to July 2021. Flow-cytometry was used to calculate specific lymphocyte subpopulations on day 1 (admission) and on day 5 of hospitalization (CD45, CD3, CD3CD8, CD3CD4, CD3CD4CD8, CD19, CD16CD56, CD34RA, CD45RO). Markers of disease severity and outcomes included: burden of disease on CT (% of affected lung parenchyma injury), C-reactive protein and interleukin-6 levels. PO2/FiO2 ratio and differences in lymphocytes subsets between two timepoints were also calculated. Logistic and linear regressions were used for the analyses. All analyses were performed using Stata (version 13.1; Stata Corp, College Station, TX, USA). Results: Higher levels of CD16CD56 cells (Natural Killer cells) were associated with higher risk of lung injury (>50% of lung parenchyma). An increase in CD3CD4 and CD4RO cell count difference between day 5 and day 1 resulted in a decrease of CRP difference between these timepoints. On the other hand, CD45RARO difference was associated with an increase in the difference of CRP levels between the two timepoints. No other significant differences were found in the rest of the lymphocyte subpopulations. Conclusions: Despite a low patient number, this study showed that alterations in lymphocyte subpopulations are associated with COVID-19 severity markers. It was observed that an increase in lymphocytes (CD4 and transiently CD45RARO) resulted in lower CRP levels, perhaps leading to COVID-19 recovery and immune response homeostasis. However, these findings need further evaluation in larger scale trials. Full article
(This article belongs to the Special Issue 10th Anniversary of Pathogens: T Cells in Pathogenic Infections)
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12 pages, 2170 KiB  
Article
Major Depressive Disorder and Pulmonary Tuberculosis Comorbidity Exacerbates Proinflammatory Immune Response—A Preliminary Study
Pathogens 2023, 12(3), 361; https://doi.org/10.3390/pathogens12030361 - 21 Feb 2023
Cited by 2 | Viewed by 1119
Abstract
Background: Major depressive disorders (MDDs) occurs frequently in patients with tuberculosis (TB). Elevated serum pro-inflammatory cytokine levels in MDD patients is a well-established fact. Therefore, an integrated clinical practice should be considered. However, the inflammatory status of MDD-TB patients is unknown. In this [...] Read more.
Background: Major depressive disorders (MDDs) occurs frequently in patients with tuberculosis (TB). Elevated serum pro-inflammatory cytokine levels in MDD patients is a well-established fact. Therefore, an integrated clinical practice should be considered. However, the inflammatory status of MDD-TB patients is unknown. In this study, we analyze cytokines in activated-cells and sera from MDD-TB, TB, MDD patients, and healthy controls. Methods: Flow cytometry was used to evaluate the intracellular production of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12, and IL-10 by peripheral blood mononuclear cells after a polyclonal stimulation. A Bio-Plex Luminex system was used to measure serum cytokine and chemokine levels in the study groups. Results: We observed a 40.6% prevalence of MDD in TB patients. The proportion of IFN-gamma-producing cells was higher in MDD-TB patients than other pathological groups. Nevertheless, the percentage of TNF-alpha- and IL-12-producing cells was similar between MDD-TB and TB patients. Likewise, MDD-TB and TB patients showed similar serum pro-inflammatory cytokine and chemokine levels, which were significantly lower than those in MDD patients. By multiple correspondence analyses, we observed that low levels of serum IL-4, IL-10, and IL-13 were powerfully associated with TB comorbidities with MDD. Conclusions: A high frequency of IFN-γ-producing cells is associated with low levels of serum anti-inflammatory cytokines in MDD-TB patients. Full article
(This article belongs to the Special Issue 10th Anniversary of Pathogens: T Cells in Pathogenic Infections)
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Review

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13 pages, 1815 KiB  
Review
T Cell Response to SARS-CoV-2 Coinfection and Comorbidities
Pathogens 2023, 12(2), 321; https://doi.org/10.3390/pathogens12020321 - 15 Feb 2023
Cited by 4 | Viewed by 3447
Abstract
For the past three years, COVID-19 has become an increasing global health issue. Adaptive immune cells, especially T cells, have been extensively investigated in regard to SARS-CoV-2 infection. However, human health and T cell responses are also impacted by many other pathogens and [...] Read more.
For the past three years, COVID-19 has become an increasing global health issue. Adaptive immune cells, especially T cells, have been extensively investigated in regard to SARS-CoV-2 infection. However, human health and T cell responses are also impacted by many other pathogens and chronic diseases. We have summarized T cell performance during SARS-CoV-2 coinfection with other viruses, bacteria, and parasites. Furthermore, we distinguished if those altered T cell statuses under coinfection would affect their clinical outcomes, such as symptom severity and hospitalization demand. T cell alteration in diabetes, asthma, and hypertension patients with SARS-CoV-2 infection was also investigated in our study. We have summarized whether changes in T cell response influence the clinical outcome during comorbidities. Full article
(This article belongs to the Special Issue 10th Anniversary of Pathogens: T Cells in Pathogenic Infections)
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27 pages, 3767 KiB  
Review
SARS-CoV-2-Specific T Cell Responses in Immunocompromised Individuals with Cancer, HIV or Solid Organ Transplants
Pathogens 2023, 12(2), 244; https://doi.org/10.3390/pathogens12020244 - 03 Feb 2023
Cited by 7 | Viewed by 2906
Abstract
Adaptive immune responses play an important role in the clinical course of SARS-CoV-2 infection. While evaluations of the virus-specific defense often focus on the humoral response, cellular immunity is crucial for the successful control of infection, with the early development of cytotoxic T [...] Read more.
Adaptive immune responses play an important role in the clinical course of SARS-CoV-2 infection. While evaluations of the virus-specific defense often focus on the humoral response, cellular immunity is crucial for the successful control of infection, with the early development of cytotoxic T cells being linked to efficient viral clearance. Vaccination against SARS-CoV-2 induces both CD4+ and CD8+ T cell responses and permits protection from severe COVID-19, including infection with the currently circulating variants of concern. Nevertheless, in immunocompromised individuals, first data imply significantly impaired SARS-CoV-2-specific immune responses after both natural infection and vaccination. Hence, these high-risk groups require particular consideration, not only in routine clinical practice, but also in the development of future vaccination strategies. In order to assist physicians in the guidance of immunocompromised patients, concerning the management of infection or the benefit of (booster) vaccinations, this review aims to provide a concise overview of the current knowledge about SARS-CoV-2-specific cellular immune responses in the vulnerable cohorts of cancer patients, people living with HIV (PLWH), and solid organ transplant recipients (SOT). Recent findings regarding the virus-specific cellular immunity in these differently immunocompromised populations might influence clinical decision-making in the future. Full article
(This article belongs to the Special Issue 10th Anniversary of Pathogens: T Cells in Pathogenic Infections)
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21 pages, 1507 KiB  
Review
Current Knowledge of Th22 Cell and IL-22 Functions in Infectious Diseases
Pathogens 2023, 12(2), 176; https://doi.org/10.3390/pathogens12020176 - 23 Jan 2023
Cited by 7 | Viewed by 2682
Abstract
T helper 22 (Th22) cells, a newly defined CD4+ T-cell lineage, are characterized by their distinct cytokine profile, which primarily consists of IL-13, IL-22 and TNF-α. Th22 cells express a wide spectrum of chemokine receptors, such as CCR4, CCR6 and CCR10. The main [...] Read more.
T helper 22 (Th22) cells, a newly defined CD4+ T-cell lineage, are characterized by their distinct cytokine profile, which primarily consists of IL-13, IL-22 and TNF-α. Th22 cells express a wide spectrum of chemokine receptors, such as CCR4, CCR6 and CCR10. The main effector molecule secreted by Th22 cells is IL-22, a member of the IL-10 family, which acts by binding to IL-22R and triggering a complex downstream signaling system. Th22 cells and IL-22 have been found to play variable roles in human immunity. In preventing the progression of infections such as HIV and influenza, Th22/IL-22 exhibited protective anti-inflammatory characteristics, and their deleterious proinflammatory activities have been demonstrated to exacerbate other illnesses, including hepatitis B and Helicobacter pylori infection. Herein, we review the current understanding of Th22 cells, including their definition, differentiation and mechanisms, and the effect of Th22/IL-22 on human infectious diseases. According to studies on Th22 cells, Th22/IL-22 may be a promising therapeutic target and an effective treatment strategy for various infections. Full article
(This article belongs to the Special Issue 10th Anniversary of Pathogens: T Cells in Pathogenic Infections)
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17 pages, 1232 KiB  
Review
The Double Game Played by Th17 Cells in Infection: Host Defense and Immunopathology
Pathogens 2022, 11(12), 1547; https://doi.org/10.3390/pathogens11121547 - 15 Dec 2022
Cited by 14 | Viewed by 4248
Abstract
T-helper 17 (Th17) cells represent a subpopulation of CD4+ T lymphocytes that play an essential role in defense against pathogens. Th17 cells are distinguished from Th1 and Th2 cells by their ability to produce members of the interleukin-17 (IL-17) family, namely IL-17A and [...] Read more.
T-helper 17 (Th17) cells represent a subpopulation of CD4+ T lymphocytes that play an essential role in defense against pathogens. Th17 cells are distinguished from Th1 and Th2 cells by their ability to produce members of the interleukin-17 (IL-17) family, namely IL-17A and IL-17F. IL-17 in turn induces several target cells to synthesize and release cytokines, chemokines, and metalloproteinases, thereby amplifying the inflammatory cascade. Th17 cells reside predominantly in the lamina propria of the mucosa. Their main physiological function is to maintain the integrity of the mucosal barrier against the aggression of infectious agents. However, in an appropriate inflammatory microenvironment, Th17 cells can transform into immunopathogenic cells, giving rise to inflammatory and autoimmune diseases. This review aims to analyze the complex mechanisms through which the interaction between Th17 and pathogens can be on the one hand favorable to the host by protecting it from infectious agents, and on the other hand harmful, potentially generating autoimmune reactions and tissue damage. Full article
(This article belongs to the Special Issue 10th Anniversary of Pathogens: T Cells in Pathogenic Infections)
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