Neutrophils in Tuberculosis: Cell Biology, Cellular Networking and Multitasking in Host Defense

Neutrophils readily infiltrate infection foci, phagocytose and usually destroy microbes. In tuberculosis (TB), a chronic pulmonary infection caused by Mycobacterium tuberculosis (Mtb), neutrophils harbor bacilli, are abundant in tissue lesions, and their abundances in blood correlate with poor disease outcomes in patients. The biology of these innate immune cells in TB is complex. Neutrophils have been assigned host-beneficial as well as deleterious roles. The short lifespan of neutrophils purified from blood poses challenges to cell biology studies, leaving intracellular biological processes and the precise consequences of Mtb–neutrophil interactions ill-defined. The phenotypic heterogeneity of neutrophils, and their propensity to engage in cellular cross-talk and to exert various functions during homeostasis and disease, have recently been reported, and such observations are newly emerging in TB. Here, we review the interactions of neutrophils with Mtb, including subcellular events and cell fate upon infection, and summarize the cross-talks between neutrophils and lung-residing and -recruited cells. We highlight the roles of neutrophils in TB pathophysiology, discussing recent findings from distinct models of pulmonary TB, and emphasize technical advances that could facilitate the discovery of novel neutrophil-related disease mechanisms and enrich our knowledge of TB pathogenesis.

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The cell biology of inflammation: From common traits to remarkable immunological adaptations

The Journal of Cell Biology ◽

10.1083/jcb.202004003 ◽

2020 ◽

Vol 219 (7) ◽

Cited By ~ 1

Author(s):

Helen Weavers ◽

Paul Martin

Keyword(s):

Innate Immunity ◽

Cell Division ◽

Membrane Trafficking ◽

Immune Cells ◽

Cell Biology ◽

Foreign Bodies ◽

Cell Types ◽

Innate Immune ◽

Innate Immune Cells ◽

Starting Point

Tissue damage triggers a rapid and robust inflammatory response in order to clear and repair a wound. Remarkably, many of the cell biology features that underlie the ability of leukocytes to home in to sites of injury and to fight infection—most of which are topics of intensive current research—were originally observed in various weird and wonderful translucent organisms over a century ago by Elie Metchnikoff, the “father of innate immunity,” who is credited with discovering phagocytes in 1882. In this review, we use Metchnikoff’s seminal lectures as a starting point to discuss the tremendous variety of cell biology features that underpin the function of these multitasking immune cells. Some of these are shared by other cell types (including aspects of motility, membrane trafficking, cell division, and death), but others are more unique features of innate immune cells, enabling them to fulfill their specialized functions, such as encapsulation of invading pathogens, cell–cell fusion in response to foreign bodies, and their self-sacrifice as occurs during NETosis.

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Mitochondrial Heterogeneity: Evaluating Mitochondrial Subpopulation Dynamics in Stem Cells

Stem Cells International ◽

10.1155/2017/7068567 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 22

Author(s):

D. C. Woods

Keyword(s):

Stem Cells ◽

Cell Fate ◽

Pluripotent Stem Cells ◽

Cell Biology ◽

Cell Types ◽

Cellular Reprogramming ◽

Cellular Functions ◽

Technical Advances ◽

Mitochondrial Heterogeneity ◽

Key Participants

Although traditionally viewed as the “powerhouse” of the cell, an accruing body of evidence in the rapidly growing field of mitochondrial biology supports additional roles of mitochondria as key participants in a multitude of cellular functions. While it has been well established that mitochondria in different tissues have distinctive ultrastructural features consistent with differential bioenergetic demands, recent and emerging technical advances in flow cytometry, imaging, and “-omics”-based bioinformatics have only just begun to explore the complex and divergent properties of mitochondria within tissues and cell types. Moreover, contemporary studies evaluating the role of mitochondria in pluripotent stem cells, cellular reprogramming, and differentiation point to a potential importance of mitochondrial subpopulations and heterogeneity in the field of stem cell biology. This review assesses the current literature regarding mitochondrial subpopulations within cell and tissue types and evaluates the current understanding of how mitochondrial diversity and heterogeneity might impact cell fate specification in pluripotent stem cells.

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Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation

Annual Review of Immunology ◽

10.1146/annurev-immunol-093019-110159 ◽

2021 ◽

Vol 39 (1) ◽

Author(s):

Marco Prinz ◽

Takahiro Masuda ◽

Michael A. Wheeler ◽

Francisco J. Quintana

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Immune Cells ◽

Cell Biology ◽

Treatment Options ◽

Myeloid Cell ◽

Innate Immune ◽

Annual Review ◽

Publication Date ◽

Innate Immune Cells

The immune system of the central nervous system (CNS) consists primarily of innate immune cells. These are highly specialized macrophages found either in the parenchyma, called microglia, or at the CNS interfaces, such as leptomeningeal, perivascular, and choroid plexus macrophages. While they were primarily thought of as phagocytes, their function extends well beyond simple removal of cell debris during development and diseases. Brain-resident innate immune cells were found to be plastic, long-lived, and host to an outstanding number of risk genes for multiple pathologies. As a result, they are now considered the most suitable targets for modulating CNS diseases. Additionally, recent single-cell technologies enhanced our molecular understanding of their origins, fates, interactomes, and functional cell states during health and perturbation. Here, we review the current state of our understanding and challenges of the myeloid cell biology in the CNS and treatment options for related diseases. Expected final online publication date for the Annual Review of Immunology, Volume 39 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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T cell fate following Salmonella infection is determined by a STING-IRF1 signaling axis in mice

Communications Biology ◽

10.1038/s42003-019-0701-2 ◽

2019 ◽

Vol 2 (1) ◽

Cited By ~ 2

Author(s):

Sung-Moo Park ◽

Tatsushi Omatsu ◽

Yun Zhao ◽

Naohiro Yoshida ◽

Pankaj Shah ◽

...

Keyword(s):

T Cell ◽

Cell Fate ◽

Bacterial Species ◽

Innate Immune ◽

Disease Mechanisms ◽

Signaling Axis ◽

Cell Cytosol ◽

Microbial C ◽

Microbial Dna ◽

Host Cell Cytosol

AbstractThe innate immune response following infection with entero-invasive bacterial species is triggered upon release of cyclic di-guanylate monophosphate (c-di-GMP) into the host cell cytosol. Bacterial c-di-GMP activates the intracellular Sensor Stimulator of Interferon Genes (STING), encoded by Tmem173 in mice. Here we identify Interferon Regulatory Factor (IRF) 1 as a critical effector of STING-mediated microbial DNA sensing that is responsible for TH17 cell generation in the mucosal immune system. We find that STING activation induces IRF1-dependent transcriptional programs in dendritic cells (DCs) that define T cell fate determination, including induction of Gasdermin D, IL-1 family member cytokines, and enzymes for eicosanoid synthesis. Our results show that IRF1-dependent transcriptional programs in DCs are a prerequisite for antigen-specific TH17 subspecification in response to microbial c-di-GMP and Salmonella typhimurium infection. Our identification of a STING-IRF1 signaling axis for adaptive host defense control will aid further understanding of infectious disease mechanisms.

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