scholarly journals Innate immunity against infectious diseases, particularly in swine

2020 ◽  
Vol 76 (2) ◽  
pp. 67-70
Author(s):  
ZYGMUNT PEJSAK ◽  
MARIAN TRUSZCZYŃSKI ◽  
KAZIMIERZ TARASIUK
Keyword(s):  
Infectious Diseases ◽  
Defense Mechanisms ◽  
Bacterial Infections ◽  
Innate Immune ◽  
Mononuclear Phagocytes ◽  
Phagocytic Cells ◽  
Host Defense Peptides ◽  
Innate Defense ◽  
Etiologic Agents ◽  
Monocytes And Macrophages

The importance of innate defense mechanisms especially refering to swine, was characterized. Physical, chemical and microbial barriers were mentioned. The role of cells was underlined in controlling infection by phagocytosis without earlier immunisation by antigens and only depending on the genome of the born animal. The two main types of phagocytic cells were evaluated in antiinfectious activity: a)granular leucocytes, including neutrophils, basophils, eosynophils and mast cells, b)mononuclear phagocytes. These include blood circulating monocytes and macrophages. It was stated that natural killer cells belonging also to innate immune system can kill bacteria and viruses participating as etiologic agents in infectious diseases. Another group of innate immune factors, not cells but molecules, are creating defensins being host defense peptides. The complement mediates the inflammatory response, controlling bacterial infections. The following antiinfectious activity is exerted by Toll-like receptors. The presented cytokines are protein or glycoprotein molecules secreted by cells. They participate in intercellular and intracellular signalling.

scholarly journals Glycobiology of syndecan-1 in bacterial infections

2018 ◽  
Vol 46 (2) ◽  
pp. 371-377 ◽  
Author(s):  
Rafael S. Aquino ◽  
Yvonne Hui-Fang Teng ◽  
Pyong Woo Park
Keyword(s):  
Cell Surface ◽  
Defense Mechanisms ◽  
Bacterial Infections ◽  
Bacterial Pathogens ◽  
Innate Immune ◽  
Host Cells ◽  
Innate Defense ◽  
Immune Clearance ◽  
Bacterial Adhesins ◽  
A Cell

Syndecan-1 (Sdc1) is a major cell surface heparan sulfate (HS) proteoglycan of epithelial cells, a cell type targeted by many bacterial pathogens early in their pathogenesis. Loss of Sdc1 in mice is a gain-of-function mutation that significantly decreases the susceptibility to several bacterial infections, suggesting that subversion of Sdc1 is an important virulence strategy. HS glycosaminoglycan (GAG) chains of cell surface Sdc1 promote bacterial pathogenesis by facilitating the attachment of bacteria to host cells. Engagement of cell surface Sdc1 HS chains by bacterial adhesins transmits signal through the highly conserved Sdc1 cytoplasmic domain, which can lead to uptake of intracellular bacterial pathogens. On the other hand, several bacteria that do not require Sdc1 for their attachment and invasion stimulate Sdc1 shedding and exploit the capacity of Sdc1 ectodomain HS GAGs to disarm innate defense mechanisms to evade immune clearance. Recent data suggest that select HS sulfate motifs, and not the overall charge of HS, are important in the inhibition of innate immune mechanisms. Here, we discuss several examples of Sdc1 subversion in bacterial infections.

scholarly journals A Superoxide-Hypersusceptible Salmonella enterica Serovar Typhimurium Mutant Is Attenuated but Regains Virulence in p47phox−/− Mice

2002 ◽  
Vol 70 (5) ◽  
pp. 2614-2621 ◽  
Author(s):  
Angela van Diepen ◽  
Tahar van der Straaten ◽  
Steven M. Holland ◽  
Riny Janssen ◽  
Jaap T. van Dissel
Keyword(s):  
Salmonella Enterica ◽  
Defense Mechanisms ◽  
Mononuclear Phagocytes ◽  
Wild Type ◽  
Phagocytic Cells ◽  
Bacterial Counts ◽  
Innate Defense ◽  
Serovar Typhimurium

ABSTRACT Salmonella enterica serovar Typhimurium is a gram-negative, facultative intracellular pathogen that predominantly invades mononuclear phagocytes and is able to establish persistent infections. One of the innate defense mechanisms of phagocytic cells is the production of reactive oxygen species, including superoxide. S. enterica serovar Typhimurium has evolved mechanisms to resist such radicals, and these mechanisms could be decisive in its ability to survive and replicate within macrophages. Recently, we described a superoxide-hypersusceptible S. enterica serovar Typhimurium mutant strain, DLG294, that carries a transposon in sspJ, resulting in the lack of expression of SspJ, which is necessary for resistance against superoxide and replication within macrophages. Here we show that DLG294, which is a 14028s derivative, hardly induced any granulomatous lesions in the livers upon subcutaneous infection of C3H/HeN (Ityr) mice with 3 × 104 bacteria and that its bacterial counts were reduced by 3 log units compared to those of wild-type S. enterica serovar Typhimurium 14028s on day 5 after infection. In contrast, DLG294 replicated like wild-type S. enterica serovar Typhimurium 14028s and induced a phenotypically similar liver pathology in p47phox−/− mice, which are deficient in the p47phox subunit of the NADPH oxidase complex and which do not produce superoxide. Consistent with these results, DLG294 reached bacterial counts identical to those of wild-type S. enterica serovar Typhimurium 14028s in bone marrow-derived macrophages from p47phox−/− mice and in X-CGD PLB-985 cells at 24 h after challenge. These results indicate that SspJ plays a role in the bacterium's resistance to oxidative stress and in the survival and replication of S. enterica serovar Typhimurium both in vitro and in vivo.

scholarly journals Impaired microbicidal capacity of mononuclear phagocytes from patients with type I Gaucher disease: partial correction by enzyme replacement therapy

Blood ◽  
1995 ◽  
Vol 86 (12) ◽  
pp. 4645-4649 ◽  
Author(s):  
L Marodi ◽  
R Kaposzta ◽  
J Toth ◽  
A Laszlo
Keyword(s):  
Gaucher Disease ◽  
Bacterial Infections ◽  
Normal Serum ◽  
Mononuclear Phagocytes ◽  
Type I ◽  
Phagocytic Cells ◽  
Oxygen Intermediates ◽  
Enzyme Replacement ◽  
Monocytes And Macrophages ◽  
Generate Superoxide Anion

The higher susceptibility to serious bacterial infections in patients with Gaucher disease (GD) may be due in part to defective function of phagocytic cells. We studied five patients with GD (type I) and examined the ability of granulocytes and mononuclear phagocytes from these patients to phagocytose and kill Staphylococcus aureus and to generate superoxide anion (O2-) on stimulation with fully opsonized bacteria. Serum-opsonized staphylococci were ingested equally by phagocytic cells from patients and controls. In the presence of normal serum, the extent of killing of S aureus and the release of O2- by granulocytes over incubation periods of 60 minutes and 30 minutes, respectively, were also equivalent for patients and controls. However, we found that killing of viable bacteria and release of O2- by the patients' monocytes was significantly lower than that in cells from controls (P < .05 for both). The magnitude of differences in killing and O2- release between patients' cells and those from controls was even more profound with monocyte-derived macrophages. Enzyme augmentation with macrophage-targeted glucocerebrosidase preparation for 6 months at doses from 7.5 to 10 U/kg/wk resulted in significant increases of functional activities and O2- generation of monocytes and macrophages along with hematologic and hepatosplenic improvements. These data suggest that mononuclear phagocytes from GD patients are defective in their ability to kill bacteria and to generate reactive oxygen intermediates. Our data also suggest that enzyme substitution may improve functions of monocytes and macrophages in patients with GD that should make them more resistant to severe bacterial infection.

scholarly journals Receptors That Inhibit Macrophage Activation: Mechanisms and Signals of Regulation and Tolerance

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Ranferi Ocaña-Guzman ◽  
Luis Vázquez-Bolaños ◽  
Isabel Sada-Ovalle
Keyword(s):  
Immune System ◽  
Cell Lines ◽  
Immune Tolerance ◽  
Defense Mechanisms ◽  
Macrophage Activation ◽  
Immunological Tolerance ◽  
Innate Defense ◽  
Activation Mechanisms ◽  
Monocytes And Macrophages ◽  
Inhibitory Molecules

A variety of receptors perform the function of attenuating or inhibiting activation of cells in which they are expressed. Examples of these kinds of receptors include TIM-3 and PD-1, among others that have been widely studied in cells of lymphoid origin and, though to a lesser degree, in other cell lines. Today, several studies describe the function of these molecules as part of the diverse mechanisms of immune tolerance that exist in the immune system. This review analyzes the function of some of these proteins in monocytes and macrophages and as well as their participation as inhibitory molecules or elements of immunological tolerance that also act in innate defense mechanisms. We chose the receptors TIM-3, PD-1, CD32b, and CD200R because these molecules have distinct functional characteristics that provide examples of the different regulating mechanisms in monocytes and macrophages.

scholarly journals The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Alexandre Giraud-Gatineau ◽  
Juan Manuel Coya ◽  
Alexandra Maure ◽  
Anne Biton ◽  
Michael Thomson ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Bacterial Infections ◽  
Bacterial Species ◽  
Innate Immune ◽  
Immune Resistance ◽  
Genome Wide ◽  
Activation Of Transcription ◽  
Wide Range ◽  
Transcription Factor Eb ◽  
Genome Wide Gene Expression

Antibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the host’s immune system. Here, we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages. Genome-wide gene expression analysis revealed that BDQ reprogramed cells into potent bactericidal phagocytes. We found that 579 and 1,495 genes were respectively differentially expressed in naive- and M. tuberculosis-infected macrophages incubated with the drug, with an over-representation of lysosome-associated genes. BDQ treatment triggered a variety of antimicrobial defense mechanisms, including phagosome-lysosome fusion, and autophagy. These effects were associated with activation of transcription factor EB, involved in the transcription of lysosomal genes, resulting in enhanced intracellular killing of different bacterial species that were naturally insensitive to BDQ. Thus, BDQ could be used as a host-directed therapy against a wide range of bacterial infections.

scholarly journals Neutral high-generation phosphorus dendrimers inhibit macrophage-mediated inflammatory response in vitro and in vivo

2017 ◽  
Vol 114 (37) ◽  
pp. E7660-E7669 ◽  
Author(s):  
I. Posadas ◽  
L. Romero-Castillo ◽  
N. El Brahmi ◽  
D. Manzanares ◽  
S. Mignani ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Autoimmune Diseases ◽  
Proinflammatory Cytokines ◽  
Biomedical Applications ◽  
Human Monocyte ◽  
Mononuclear Phagocytes ◽  
Monocytes And Macrophages ◽  
Potential Applications

Inflammation is part of the physiological response of the organism to infectious diseases caused by organisms such as bacteria, viruses, fungi, or parasites. Innate immunity, mediated by mononuclear phagocytes, including monocytes and macrophages, is a first line of defense against infectious diseases and plays a key role triggering the delayed adaptive response that ensures an efficient defense against pathogens. Monocytes and macrophages stimulation by pathogen antigens results in activation of different signaling pathways leading to the release of proinflammatory cytokines. However, inflammation can also participate in the pathogenesis of several diseases, the autoimmune diseases that represent a relevant burden for human health. Dendrimers are branched, multivalent nanoparticles with a well-defined structure that have a high potential for biomedical applications. To explore new approaches to fight against the negative aspects of inflammation, we have used neutral high-generation phosphorus dendrimers bearing 48 (G3) or 96 (G4) bisphosphonate groups on their surface. These dendrimers show no toxicity and have good solubility and chemical stability in aqueous solutions. Here, we present data indicating that neutral phosphorus dendrimers show impressive antiinflammatory activities both in vitro and in vivo. In vitro, these dendrimers reduced the secretion of proinflammatory cytokines from mice and human monocyte-derived macrophages. In addition, these molecules present efficient antiinflammatory activity in vivo in a mouse model of subchronic inflammation. Taken together, these data suggest that neutral G3-G4 phosphorus dendrimers have strong potential applications in the therapy of inflammation and, likely, of autoimmune diseases.

scholarly journals Salmonella and Reactive Oxygen Species: A Love-Hate Relationship

2019 ◽  
Vol 11 (3) ◽  
pp. 216-226 ◽  
Author(s):  
Mikael Rhen
Keyword(s):  
Reactive Oxygen ◽  
Immune Defense ◽  
Innate Immune ◽  
Intracellular Pathogens ◽  
Oxygen Species ◽  
Phagocytic Cells ◽  
Innate Defense ◽  
Innate Immune Defense ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Salmonella enterica represents an enterobacterial species including numerous serovars that cause infections at, or initiated at, the intestinal epithelium. Many serovars also act as facultative intracellular pathogens with a tropism for phagocytic cells. These bacteria not only survive in phagocytes but also undergo de facto replication therein. Phagocytes, through the activities of phagocyte NADPH-dependent oxidase and inducible nitric oxide synthase, are very proficient in converting molecular oxygen to reactive oxygen (ROS) and nitrogen species (RNS). These compounds represent highly efficient effectors of the innate immune defense. Salmonella is by no means resistant to these effectors, which may stand in contrast to the host niches chosen. To cope with this paradox, these bacteria rely on an array of detoxification and repair systems. Combination these systems allows for a high enough tolerance to ROS and RNS to enable establishment of infection. In addition, salmonella possesses protein factors that have the potential to dampen the infection-associated inflammation, which evidently results in a reduced exposure to ROS and RNS. This review attempts to summarize the activities and strategies by which salmonella tries to cope with ROS and RNS and how the bacterium can make use of these innate defense factors.

scholarly journals Subversion of host defense mechanisms by murine tumors. I. A circulating factor that suppresses macrophage-mediated resistance to infection.

1976 ◽  
Vol 143 (3) ◽  
pp. 559-573 ◽  
Author(s):  
R J North ◽  
D P Kirstein ◽  
R L Tuttle
Keyword(s):  
Defense Mechanisms ◽  
Physiological Activity ◽  
Mononuclear Phagocytes ◽  
Antibacterial Resistance ◽  
Phagocytic Cells ◽  
Small Molecular Weight ◽  
Suppressor Factor ◽  
Murine Tumors ◽  
Resistance To Infection ◽  
Tumor Bearer

The subcutaneous injection of cells of any one of five unselected murine tumors resulted very rapidly in the liberation into the circulation of a small molecular weight factor that severely impaired the capacity of the host to resist experimental infection with Listeria monocytogenes and Yersinia enterocolitica. It was found that the factor appeared in blood within 8 h of injecting tumor cells subcutaneously. That it possessed potent physiological activity was evidenced by the demonstration that an infusion of as little as 0.015 ml of tumor-bearer serum strikingly suppressed the capacity of normal recipients to resist bacterial infection. It was reasoned on the basis of the knowledge that the only cells in mice with the capacity to destroy Listeria are macrophages, that suppression of antibacterial resistance was caused by the ability of the tumor-suppressor factor to interfere, either directly or indirectly, with the antibacterial functions of these mononuclear phagocytic cells. The results are consistent with the hypothesis that at least some malignant neoplastic cells are naturally selected to avoid destruction by native and acquired antitumor mechanisms of mononuclear phagocytes.

scholarly journals High Innate Immune Specificity through Diversified C-Type Lectin-Like Domain Proteins in Invertebrates

2015 ◽  
Vol 8 (2) ◽  
pp. 129-142 ◽  
Author(s):  
Barbara Pees ◽  
Wentao Yang ◽  
Alejandra Zárate-Potes ◽  
Hinrich Schulenburg ◽  
Katja Dierking
Keyword(s):  
Immune System ◽  
Protein Function ◽  
Innate Immune System ◽  
Defense Mechanisms ◽  
Innate Immune ◽  
Innate Defense ◽  
C Elegans ◽  
Current State ◽  
Gene Diversification

A key question in current immunity research is how the innate immune system can generate high levels of specificity. Evidence is accumulating that invertebrates, which exclusively rely on innate defense mechanisms, can differentiate between pathogens on the species and even strain level. In this review, we identify and discuss the particular potential of C-type lectin-like domain (CTLD) proteins to generate high immune specificity. Whilst several CTLD proteins are known to act as pattern recognition receptors in the vertebrate innate immune system, the exact role of CTLD proteins in invertebrate immunity is much less understood. We show that CTLD genes are highly abundant in most metazoan genomes and summarize the current state of knowledge on CTLD protein function in insect, crustacean and nematode immune systems. We then demonstrate extreme CTLD gene diversification in the genomes of Caenorhabditis nematodes and provide an update of data from CTLD gene function studies in C. elegans, which indicate that the diversity of CTLD genes could contribute to immune specificity. In spite of recent achievements, the exact functions of the diversified invertebrate CTLD genes are still largely unknown. Our review therefore specifically discusses promising research approaches to rectify this knowledge gap.

scholarly journals Immune surveillance of the lung by migrating tissue monocytes

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Mathieu P Rodero ◽  
Lucie Poupel ◽  
Pierre-Louis Loyher ◽  
Pauline Hamon ◽  
Fabrice Licata ◽  
...  
Keyword(s):  
Steady State ◽  
Immune Surveillance ◽  
Innate Immune ◽  
Mononuclear Phagocytes ◽  
Effector Cells ◽  
State Surveillance ◽  
Monocytes And Macrophages ◽  
Lung Capillaries ◽  
Large Vessels ◽  
Inflammatory Tissue

Monocytes are phagocytic effector cells in the blood and precursors of resident and inflammatory tissue macrophages. The aim of the current study was to analyse and compare their contribution to innate immune surveillance of the lung in the steady state with macrophage and dendritic cells (DC). ECFP and EGFP transgenic reporters based upon Csf1r and Cx3cr1 distinguish monocytes from resident mononuclear phagocytes. We used these transgenes to study the migratory properties of monocytes and macrophages by functional imaging on explanted lungs. Migratory monocytes were found to be either patrolling within large vessels of the lung or locating at the interface between lung capillaries and alveoli. This spatial organisation gives to monocytes the property to capture fluorescent particles derived from both vascular and airway routes. We conclude that monocytes participate in steady-state surveillance of the lung, in a way that is complementary to resident macrophages and DC, without differentiating into macrophages.

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