Insect renal tubules constitute a cell-autonomous immune system that protects the organism against bacterial infection

During the ongoing global pandemic of coronavirus disease 2019 (COVID-19), the benefit of treating patients with cancer must be weighed against the COVID-19 infection risks to patients, staff and society. Prostate cancer is one of the most common cancers among men and raises particular interest during the pandemic as recent reports show that the TMPRSS2 (and other serine proteases), which facilitate the entry, replication and budding of the virion from a cell, can be inhibited using androgen deprivation therapy. Nevertheless, patients with metastatic prostate cancer commonly receive chemotherapy which may compromise their immune system. This paper aims to address the current status of the COVID-19 in patients with cancer overall and suggests an optimal approach to patients with metastatic prostate cancer.

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Neisseria gonorrhoeae Porin P1.B Induces Endosome Exocytosis and a Redistribution of Lamp1 to the Plasma Membrane

Infection and Immunity ◽

10.1128/iai.70.11.5965-5971.2002 ◽

2002 ◽

Vol 70 (11) ◽

pp. 5965-5971 ◽

Cited By ~ 16

Author(s):

Patricia Ayala ◽

Brandi Vasquez ◽

Lee Wetzler ◽

Magdalene So

Keyword(s):

Plasma Membrane ◽

Epithelial Cells ◽

Cell Surface ◽

Neisseria Gonorrhoeae ◽

Bacterial Infection ◽

Immunoglobulin A ◽

Late Endosomes ◽

A Cell ◽

Iga Protease

ABSTRACT The immunoglobulin A (IgA) protease secreted by pathogenic Neisseria spp. cleaves Lamp1, thereby altering lysosomes in a cell and promoting bacterial intracellular survival. We sought to determine how the IgA protease gains access to cellular Lamp1 in order to better understand the role of this cleavage event in bacterial infection. In a previous report, we demonstrated that the pilus-induced Ca2+ transient triggers lysosome exocytosis in human epithelial cells. This, in turn, increases the level of Lamp1 at the plasma membrane, where it can be cleaved by IgA protease. Here, we show that porin also induces a Ca2+ flux in epithelial cells. This transient is similar in nature to that observed in phagocytes exposed to porin. In contrast to the pilus-induced Ca2+ transient, the porin-induced event does not trigger lysosome exocytosis. Instead, it stimulates exocytosis of early and late endosomes and increases Lamp1 on the cell surface. These results indicate that Neisseria pili and porin perturb Lamp1 trafficking in epithelial cells by triggering separate and distinct Ca2+-dependent exocytic events, bringing Lamp1 to the cell surface, where it can be cleaved by IgA protease.

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Understanding GroEL and DnaK Stress Response Proteins as Antigens for Bacterial Diseases

Vaccines ◽

10.3390/vaccines8040773 ◽

2020 ◽

Vol 8 (4) ◽

pp. 773

Author(s):

Kezia R. Fourie ◽

Heather L. Wilson

Keyword(s):

Immune System ◽

Stress Response ◽

Cell Surface ◽

Virulence Factors ◽

Cellular Localization ◽

Vaccine Development ◽

Host Immune System ◽

A Cell ◽

Stress Response Proteins ◽

Shock Proteins

Bacteria do not simply express a constitutive panel of proteins but they instead undergo dynamic changes in their protein repertoire in response to changes in nutritional status and when exposed to different environments. These differentially expressed proteins may be suitable to use for vaccine antigens if they are virulence factors. Immediately upon entry into the host organism, bacteria are exposed to a different environment, which includes changes in temperature, osmotic pressure, pH, etc. Even when an organism has already penetrated the blood or lymphatics and it then enters another organ or a cell, it can respond to these new conditions by increasing the expression of virulence factors to aid in bacterial adherence, invasion, or immune evasion. Stress response proteins such as heat shock proteins and chaperones are some of the proteins that undergo changes in levels of expression and/or changes in cellular localization from the cytosol to the cell surface or the secretome, making them potential immunogens for vaccine development. Herein we highlight literature showing that intracellular chaperone proteins GroEL and DnaK, which were originally identified as playing a role in protein folding, are relocated to the cell surface or are secreted during invasion and therefore may be recognized by the host immune system as antigens. In addition, we highlight literature showcasing the immunomodulation effects these proteins can have on the immune system, also making them potential adjuvants or immunotherapeutics.

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Synbiotic application to enhance growth, immune system, and disease resistance toward bacterial infection in catfish (Clarias gariepinus)

Aquaculture ◽

10.1016/j.aquaculture.2021.737794 ◽

2022 ◽

Vol 549 ◽

pp. 737794

Author(s):

Esti Handayani Hardi ◽

Rudy Agung Nugroho ◽

Rita Rostika ◽

Choirum M. Mardliyaha ◽

Komsanah Sukarti ◽

...

Keyword(s):

Disease Resistance ◽

Immune System ◽

Bacterial Infection ◽

Clarias Gariepinus

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The Innate Immune System Favors Emergency Monopoiesis at the Expense of DC Differentiation to Control Bacterial Infections

Blood ◽

10.1182/blood.v124.21.2722.2722 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2722-2722

Author(s):

Kristin Bieber ◽

Karina A. Pasquevich ◽

Manina Günter ◽

Matthias Grauer ◽

Oliver Pötz ◽

...

Keyword(s):

Immune System ◽

Bacterial Infection ◽

Bacterial Infections ◽

Conflicts Of Interest ◽

Bacterial Load ◽

Innate Immune ◽

General Response ◽

The Impact ◽

Myeloid Progenitors

Abstract Dendritic cells (DCs) are critical in host defense against infection, bridging the innate and adaptive immune system. Patients with sepsis display reduced circulating and splenic DCs and impaired DC function that may contribute to prolonged immune suppression and exacerbation of infection. However, the mechanisms of pathogen-induced DC depletion remain poorly understood. Here, a mouse model of systemic bacterial infection was employed to analyze the impact of different bacterial pathogens on DC development in vivo. We found that the numbers of bone marrow (BM) hematopoietic progenitors committed to the DC lineages were reduced following systemic infection with different Gram-positive and Gram-negative bacteria. In parallel, a TLR4-dependent increase of committed monocyte progenitors in the BM as well as mature monocytes in the spleen was observed. In line, adoptively transferred FLT3+ myeloid progenitors (MPs) developed preferentially to monocytes at the expense of DCs in infected animals. Analyses performed on mixed BM chimeras suggested that both the reduction of DC progenitors and the induction of monopoiesis following infection were dependent on extrinsic TLR4 signaling driving the secretion of IFN-g regulated chemokines. Consistently, these effects were completely abrogated by suppression of IFN-g signaling. Elevated monocyte numbers in the spleen triggered by infection were due to a CCR2-dependent egress from the BM. In CCR2-deficient mice, in which monocytosis reportedly is abrogated, we observed a significantly increased bacterial load in the spleen and a reduced survival rate, highlighting the importance of monocytes for bacterial clearance. Together, our data provide evidence for a general response of myeloid progenitors upon bacterial infection to enhance monocyte production, thereby increasing the availability of innate immune cells as a first line of defense against invading pathogens. Concomitantly the development of DCs is impaired, which may be responsible for transient immunosuppression in e.g. bacterial sepsis. Disclosures No relevant conflicts of interest to declare.

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Immune Monitoring upon Treatment with Biologics in Sjögren’s Syndrome: The What, Where, When, and How

Biomolecules ◽

10.3390/biom11010116 ◽

2021 ◽

Vol 11 (1) ◽

pp. 116

Author(s):

Joyce J.B.C. van Beers ◽

Jan G.M.C. Damoiseaux

Keyword(s):

Immune System ◽

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Immune Monitoring ◽

Soluble Factor ◽

Adverse Side Effects ◽

A Cell ◽

Sjögren‘S Syndrome

Over the years, a wide variety of therapeutic antibodies has been successfully introduced in the auto-immunology clinic, and many more are on the way. Many of these treatments address either a pathogenic circulating molecule or a cell-bound molecule. Whereas addressing the former target results in neutralization of the soluble factor and binding to the latter target either inhibits cellular function or induces selective cell death. If this targeted molecule or cell is part of the immune system, this therapy evokes a state of immunodeficiency with infections as a possible consequence. Therefore, immune monitoring is needed to prevent such adverse side effects of immunotherapy. In this paper, different immunotherapies used in Sjögren’s syndrome, as well as different approaches to monitoring the immune system, are discussed.

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NANOG helps cancer cells escape NK cell attack by downregulating ICAM1 during tumorigenesis

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1429-z ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 6

Author(s):

Kotaro Saga ◽

Jinhee Park ◽

Keisuke Nimura ◽

Norihiko Kawamura ◽

Airi Ishibashi ◽

...

Keyword(s):

Immune System ◽

Nk Cells ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Nk Cell ◽

Scid Mice ◽

High Recurrence Rate ◽

P300 Binding ◽

Related Transcription Factor ◽

A Cell

Abstract Background At the beginning of tumorigenesis, newly born cancer cells must successfully avoid attack by the immune system. Although most abnormal cells are efficiently identified and destroyed by the immune system, particularly by NK cells, the molecular mechanisms by which newly born cancer cells evade NK cell surveillance are not fully understood. Methods NK cell resistance of highly tumorigenic population of human prostate cancer (PCa) cells were confirmed by xenograft in SCID mice with or without NK cell neutralization. The mechanisms by which the tumorigenic PCa cells evaded NK cell attack were investigated by RNAseq, ChIPseq, generation of several transformants and xenograft in SCID mice. Results Here, we show that PCa cells have a strengthened ability to escape NK cell attack due to NANOG, a pluripotent-related transcription factor, mediating the repression of ICAM1, a cell adhesion molecule, during tumorigenesis. Mechanistically, NANOG directly binds to the region upstream of ICAM1. As the binding between NANOG and the upstream ICAM1 region increases, p300 binding to this region is diminished, resulting in decreased ICAM1 expression. High NANOG expression confers PCa cells the ability to resist NK cell attack via the repression of ICAM1. Consistent with these results, low ICAM1 expression is significantly correlated with a high recurrence rate in patients with PCa. Conclusions Our findings indicate that repression of ICAM1 is a critical mechanism by which cancer cells evade attack from NK cells during tumorigenesis. These results suggest a pivotal role of NANOG in establishing a gene expression profile for escaping the immune system.

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MCPIP1 RNase and Its Multifaceted Role

International Journal of Molecular Sciences ◽

10.3390/ijms21197183 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7183

Author(s):

Richard Musson ◽

Weronika Szukała ◽

Jolanta Jura

Keyword(s):

Immune System ◽

Inflammatory Mediators ◽

Physiological Response ◽

Skin Inflammation ◽

Monocyte Chemoattractant ◽

Monocyte Chemoattractant Protein ◽

A Cell ◽

Subsequent Activation ◽

Post Transcriptional Regulation

Inflammation is an organism’s physiological response to harmful septic and aseptic stimuli. This process begins locally through the influx of immune system cells to the damaged tissue and the subsequent activation and secretion of inflammatory mediators to restore homeostasis in the organism. Inflammation is regulated at many levels, and one of these levels is post-transcriptional regulation, which controls the half-life of transcripts that encode inflammatory mediators. One of the proteins responsible for controlling the amount of mRNA in a cell is the RNase monocyte chemoattractant protein-induced protein 1 (MCPIP1). The studies conducted so far have shown that MCPIP1 is involved not only in the regulation of inflammation but also in many other physiological and pathological processes. This paper provides a summary of the information on the role of MCPIP1 in adipogenesis, angiogenesis, cell differentiation, cancer, and skin inflammation obtained to date.

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Lymphoid–Epithelial Secretory Immune System in Human Fetuses in the Second Trimester of Gestation

Pediatric and Developmental Pathology ◽

10.1007/s10024-001-0088-0 ◽

2002 ◽

Vol 5 (1) ◽

pp. 22-28 ◽

Cited By ~ 4

Author(s):

Pavel Gurevich ◽

Herzl Ben-Hur ◽

Sergio Szvalb ◽

Moisey Moldavsky ◽

Itshak Zusman

Keyword(s):

Immune System ◽

Acute Infection ◽

Secretory Component ◽

Immunocompetent Cells ◽

Renal Tubules ◽

Fallopian Tubes ◽

Human Fetuses ◽

Second Trimester ◽

Internal Organs ◽

J Chain

The development of the secretory immune system (SIS) in the respiratory, digestive, and urogenital tracts and other organs of fetuses in the second trimester of gestation is described. Tissues of all internal organs of human fetuses ( n = 36) that had died between 13 and 25 weeks of gestation were studied immunohistochemically for the presence of secretory component (SC), J chain, IgA, IgM, IgG, macrophages, and different subsets of lymphocytes. We found protein elements of the SIS in fetuses during the entire second trimester in the epithelium of the digestive, respiratory, and urinary tracts; in hepatocytes; in the epithelium of the bile duct, renal tubules, and all the urinary tract; in the salivary glands, pancreas, and thyroid; in the epithelium of the Fallopian tubes and uterus; in the epididymis and the rete testes; in the skin; and in other organs. Immunocompetent cells, including IgA- and IgM-secreting cells, were located in these organs under the epithelium and sometimes between epithelial cells. In fetuses with acute infection, the number of immunocompetent cells was higher, reflecting a whole–immune system reaction, including the SIS. We conclude that the fetal SIS is a ramified, defensive immune system that is distributed throughout most organs of epithelial origin in second-trimester fetuses, and that it reacts against intrafetal infiltration by foreign antigens.

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