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Neutrophil Subsets and Polarization in Inflammation: Implications for Pathogenesis
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Neutrophil Subsets and Polarization in Inflammation: Implications for Pathogenesis

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (25 July 2022) | Viewed by 12309

Special Issue Editor

Dr. Khalil Karimi

E-Mail Website
Guest Editor
Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada
Interests: immunobiology of innate immune components such as dendritic cells, natural killer cells, and neutrophils; mechanisms of innate immunity in lung; modulation of innate lymphoid cells by myeloid cells in infection and inflammation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammatory reactions can be triggered by pathogens, cancers, and autoimmune conditions. Situations in which the inflammatory response fails to return to homeostasis can lead to immunopathological events.

Many innate immune cells are involved in the process of inflammatory responses, including neutrophils. Accumulating evidence suggests that neutrophils are highly versatile and display functional plasticity. Therefore, neutrophils are now increasingly acknowledged as important players in homeostatic conditions, as well as in pathological inflammation. For instance, neutrophils have been implicated in influencing carcinogenesis both positively and negatively. Similarly, they have exhibited both antiviral effects as well as undesirable host damage during viral infections.

Although the concept of neutrophil heterogeneity and plasticity is now well established, the multifunctional roles that neutrophil subsets and neutrophil polarization may play during inflammation and immune responses remains unclear. Dissecting factors such as key microenvironmental cues and cell-to-cell communications that could be influencing the phenotype and behavior of neutrophils is essential. This could have significant impacts on our understanding of neutrophil functionality and polarization during inflammation and on our ability to treat different inflammatory reactions.

The aim of this Special Issue of Cells is to facilitate a better understanding of how distinct inflammatory conditions shape neutrophil heterogenicity, plasticity, and functions that result in the contribution to overall pathogenesis or to resolution and restoration of the condition, with an emphasis on advancing the next generation of anti-inflammatory therapies.

Dr. Khalil Karimi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neutrophil heterogeneity and plasticity
  • neutrophil polarization
  • neutrophil subsets
  • neutrophils and microbiota
  • neutrophils in respiratory viral infections
  • neutrophils in cancer and autoimmune diseases
  • neutrophils and mucosal homeostasis

Published Papers (5 papers)

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Research

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19 pages, 4705 KiB  
Article
Dendritic Cell-Based Vaccines Recruit Neutrophils to the Local Draining Lymph Nodes to Prime Natural Killer Cell Responses
by Lily Chan, Yeganeh Mehrani, Geoffrey A. Wood, Byram W. Bridle and Khalil Karimi
Cells 2023, 12(1), 121; https://doi.org/10.3390/cells12010121 - 28 Dec 2022
Cited by 3 | Viewed by 1915
Abstract
Dendritic cell (DC)-based cancer vaccines are a form of immunotherapy that activates the innate and adaptive immune systems to combat cancers. Neutrophils contribute to cancer biology and have the potential to be exploited by immunotherapeutic platforms to enhance anti-tumor immune responses. We previously [...] Read more.
Dendritic cell (DC)-based cancer vaccines are a form of immunotherapy that activates the innate and adaptive immune systems to combat cancers. Neutrophils contribute to cancer biology and have the potential to be exploited by immunotherapeutic platforms to enhance anti-tumor immune responses. We previously showed that DC vaccines elicit the expansion of mouse interferon (IFN)γ-producing mature natural killer (NK) cells to elevate anti-tumor responses. Here, we demonstrate the rapid recruitment of neutrophils to the draining lymph nodes of DC-vaccinated mice. This was accompanied by an increase in the total number of NK cells producing IFNγ and expressing CD107a, a marker of degranulation that demonstrates NK cell functional activity. Furthermore, the depletion of neutrophils in DC-immunized mice resulted in decreased numbers of NK cells in draining lymph nodes compared to the controls. Interestingly, the increased number of IFNγ- and CD107a-expressing NK cells in DC-immunized mice was not detected in mice depleted of neutrophils. Further investigations showed that DC vaccines induced IFNγ− and TNFα-producing CD8+ T cells that also expressed CD107a, but depletion of neutrophils did not have any impact on the CD8+ T cell population. Our findings suggest that neutrophil-mediated anti-tumor immunity induced by a DC vaccine platform could be targeted to provide innovative strategies to enhance its clinical efficacy. Full article
(This article belongs to the Special Issue Neutrophil Subsets and Polarization in Inflammation: Implications for Pathogenesis)
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18 pages, 2702 KiB  
Article
Multiple Death Pathways of Neutrophils Regulate Alveolar Macrophage Proliferation
by Xiaochen Gao, Weijia Zhang, Nan Zhang, Qing Yu, Jie Su, Ke Wang, Yanru Chen, Zhen F. Fu and Min Cui
Cells 2022, 11(22), 3633; https://doi.org/10.3390/cells11223633 - 16 Nov 2022
Viewed by 1822
Abstract
Alveolar macrophage (AM) proliferation and self-renewal play an important role in the lung tissue microenvironment. However, the impact of immune cells, especially the neutrophils, on AM homeostasis or function is not well characterized. In this study, we induced in vivo migration of neutrophils [...] Read more.
Alveolar macrophage (AM) proliferation and self-renewal play an important role in the lung tissue microenvironment. However, the impact of immune cells, especially the neutrophils, on AM homeostasis or function is not well characterized. In this study, we induced in vivo migration of neutrophils into bronchoalveolar lavage (BAL) fluid and lung using CXCL1, and then co-cultured these with AMs in vitro. Neutrophils in the BAL (BAL−neutrophils), rather than neutrophils of bone marrow (BM-neutrophils), were found to inhibit AM proliferation. Analysis of publicly available data showed high heterogeneity of lung neutrophils with distinct molecular signatures of BM− and blood−neutrophils. Unexpectedly, BAL−neutrophils from influenza virus PR8-infected mice (PR8−neutrophils) did not inhibit the proliferation of AMs. Bulk RNA sequencing further revealed that co-culture of AMs with PR8−neutrophils induced IFN-α and -γ responses and inflammatory response, and AMs co-cultured with BAL−neutrophils showed higher expression of metabolism- and ROS-associated genes; in addition, BAL−neutrophils from PR8-infected mice modulated AM polarization and phagocytosis. BAL−neutrophil-mediated suppression of AM proliferation was abrogated by a combination of inhibitors of different neutrophil death pathways. Collectively, our findings suggest that multiple cell death pathways of neutrophils regulate the proliferation of AMs. Targeting neutrophil death may represent a potential therapeutic strategy for improving AM homeostasis during respiratory diseases. Full article
(This article belongs to the Special Issue Neutrophil Subsets and Polarization in Inflammation: Implications for Pathogenesis)
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15 pages, 2389 KiB  
Article
High Presence of NETotic Cells and Neutrophil Extracellular Traps in Vaginal Discharges of Women with Vaginitis: An Exploratory Study
by Fabiola Zambrano, Angélica Melo, Rodrigo Rivera-Concha, Mabel Schulz, Pamela Uribe, Flery Fonseca-Salamanca, Ximena Ossa, Anja Taubert, Carlos Hermosilla and Raúl Sánchez
Cells 2022, 11(20), 3185; https://doi.org/10.3390/cells11203185 - 11 Oct 2022
Cited by 5 | Viewed by 2613
Abstract
Infectious vaginitis is a microbiological syndrome of great importance in public health that affects millions of women worldwide. However, no studies have explored the phenomenon of the production of the neutrophil extracellular traps (NETs) that are released into the female reproductive tract in [...] Read more.
Infectious vaginitis is a microbiological syndrome of great importance in public health that affects millions of women worldwide. However, no studies have explored the phenomenon of the production of the neutrophil extracellular traps (NETs) that are released into the female reproductive tract in these pathologies. This study aimed to determine the presence of NETosis in vaginal discharges of women with bacterial vaginosis, candidiasis, and trichomoniasis by characterizing NETs. Extracellular DNA with neutrophil elastase and citrullinated histones was identified to confirm the NET components (n = 10). The concentration, phenotypes of NETs, and number of NETotic cells were determined. The results showed an increase in NETotic cells in women with Candida albicans (CA) and Trichomonas vaginalis (TV) and an increase in NETs in TV-induced vaginitis. Samples of CA- and TV-infected women showed different NET phenotypes (diffNETs, sprNETs, and aggNETs); diffNETs were found in high concentrations in samples with CA and were increased in three types of NETs in TV infections. Samples with intermediate microbiota and bacterial vaginosis showed increased NETotic cells while the intermediate microbiota presented a higher concentration of NETs. Therefore, alterations in the microbiota and the presence of fungal and parasitic infections are important stimuli for the activation and induction of NETosis, and their cytotoxic effects could enhance tissue damage. Full article
(This article belongs to the Special Issue Neutrophil Subsets and Polarization in Inflammation: Implications for Pathogenesis)
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15 pages, 3709 KiB  
Article
The Role of Neutrophils in Oncolytic Orf Virus-Mediated Cancer Immunotherapy
by Jessica A. Minott, Jacob P. van Vloten, Lily Chan, Yeganeh Mehrani, Byram W. Bridle and Khalil Karimi
Cells 2022, 11(18), 2858; https://doi.org/10.3390/cells11182858 - 14 Sep 2022
Cited by 2 | Viewed by 2065
Abstract
Neutrophils are innate leukocytes with diverse effector functions that allow them to respond to pathogens rapidly. Accumulating evidence has highlighted these cells’ complex roles in the host’s response to viral infections and tumor progression. Oncolytic virotherapy is emerging as a promising treatment modality [...] Read more.
Neutrophils are innate leukocytes with diverse effector functions that allow them to respond to pathogens rapidly. Accumulating evidence has highlighted these cells’ complex roles in the host’s response to viral infections and tumor progression. Oncolytic virotherapy is emerging as a promising treatment modality in the armamentarium of cancer therapeutics. Oncolytic viruses preferentially kill cancer cells and stimulate tumor-associated inflammation, resulting in tumor regression. Assessing the activity of individual effector cell subsets following oncolytic virotherapy is important in identifying their contribution to antitumor immunity. In this study, we investigated the role of neutrophils in oncolytic Orf-virus-mediated immunotherapy in a murine model of pulmonary melanoma metastases. The systemic administration of the Orf virus stimulated a dramatic increase in the number of leukocytes in circulation and within the tumor microenvironment, most of which were neutrophils. Analysis of tumor-burdened lungs shortly after therapy revealed significant numbers of phenotypically immature neutrophils, with the enhanced expression of molecules affiliated with activation, migration, and cytotoxicity. Neutrophils stimulated by Orf virus therapy were directly tumoricidal through tumor necrosis factor-α-mediated effects and were required for optimal antitumor efficacy following Orf virus therapy. Taken together, these data reveal neutrophils as a crucial innate effector to consider when investigating oncolytic virotherapy. Full article
(This article belongs to the Special Issue Neutrophil Subsets and Polarization in Inflammation: Implications for Pathogenesis)
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Review

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29 pages, 1444 KiB  
Review
Neutrophil Functional Heterogeneity and Implications for Viral Infections and Treatments
by Lily Chan, Solmaz Morovati, Negar Karimi, Kasra Alizadeh, Sierra Vanderkamp, Julia E. Kakish, Byram W. Bridle and Khalil Karimi
Cells 2022, 11(8), 1322; https://doi.org/10.3390/cells11081322 - 13 Apr 2022
Cited by 7 | Viewed by 3106
Abstract
Evidence suggests that neutrophils exert specialized effector functions during infection and inflammation, and that these cells can affect the duration, severity, and outcome of the infection. These functions are related to variations in phenotypes that have implications in immunoregulation during viral infections. Although [...] Read more.
Evidence suggests that neutrophils exert specialized effector functions during infection and inflammation, and that these cells can affect the duration, severity, and outcome of the infection. These functions are related to variations in phenotypes that have implications in immunoregulation during viral infections. Although the complexity of the heterogeneity of neutrophils is still in the process of being uncovered, evidence indicates that they display phenotypes and functions that can assist in viral clearance or augment and amplify the immunopathology of viruses. Therefore, deciphering and understanding neutrophil subsets and their polarization in viral infections is of importance. In this review, the different phenotypes of neutrophils and the roles they play in viral infections are discussed. We also examine the possible ways to target neutrophil subsets during viral infections as potential anti-viral treatments. Full article
(This article belongs to the Special Issue Neutrophil Subsets and Polarization in Inflammation: Implications for Pathogenesis)
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