scholarly journals The Role of ST2 Receptor in the Regulation of Brucella abortus Oral Infection

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 328
Author(s):  
Raiany Santos ◽  
Priscila C. Campos ◽  
Marcella Rungue ◽  
Victor Rocha ◽  
David Santos ◽  
...  
Keyword(s):  
Intestinal Permeability ◽  
Knockout Mice ◽  
Brucella Abortus ◽  
Immune Modulation ◽  
Oral Infection ◽  
Infection Model ◽  
Bacterial Colony ◽  
Epithelium Regeneration ◽  
St2 Receptor

The ST2 receptor plays an important role in the gut such as permeability regulation, epithelium regeneration, and promoting intestinal immune modulation. Here, we studied the role of ST2 receptor in a murine model of oral infection with Brucella abortus, its influence on gut homeostasis and control of bacterial replication. Balb/c (wild-type, WT) and ST2 deficient mice (ST2−/−) were infected by oral gavage and the results were obtained at 3 and 14 days post infection (dpi). Our results suggest that ST2−/− are more resistant to B. abortus infection, as a lower bacterial colony-forming unit (CFU) was detected in the livers and spleens of knockout mice, when compared to WT. Additionally, we observed an increase in intestinal permeability in WT-infected mice, compared to ST2−/− animals. Breakage of the intestinal epithelial barrier and bacterial dissemination might be associated with the presence of the ST2 receptor; since, in the knockout mice no change in intestinal permeability was observed after infection. Together with enhanced resistance to infection, ST2−/− produced greater levels of IFN-γ and TNF-α in the small intestine, compared to WT mice. Nevertheless, in the systemic model of infection ST2 plays no role in controlling Brucella replication in vivo. Our results suggest that the ST2 receptor is involved in the invasion process of B. abortus by the mucosa in the oral infection model.

scholarly journals Natural defense by saliva and mucosa against oral infection by Leptospira

2014 ◽  
Vol 60 (6) ◽  
pp. 383-389 ◽  
Author(s):  
Tatsuma Asoh ◽  
Mitsumasa Saito ◽  
Sharon Y.A.M. Villanueva ◽  
Takaaki Kanemaru ◽  
Nina Gloriani ◽  
...  
Keyword(s):  
Drinking Water ◽  
Gastric Acid ◽  
Human Saliva ◽  
Oral Infection ◽  
Infection Model ◽  
First Line ◽  
Pathogenic Leptospira ◽  
Natural Defense ◽  
Infection Resistance

Leptospirosis caused by drinking water has not been as frequently reported as percutaneous infection. Resistance to oral infection by pathogenic Leptospira was examined in an experimental hamster infection model. The results suggested some natural defenses against oral infection by Leptospira. First, we found that characteristic linear agglutination of Leptospira rapidly occurs when mixed with human saliva. That human saliva attenuated the infectivity of the treated leptospires by its agglutination activity suggested saliva to be the first line of defense against oral infection by leptospires. Second, only 101 Leptospira organisms caused death after submucosal injection into oral mucosa in hamsters, but oral infection with drinking water containing 105 organisms/mL did not cause death. This result showed that the mucosa plays the role of a physical barrier. Third, hamsters intragastrically infected by leptospires, with doses lethal to hamsters in oral infection, showed no signs of illness, which suggested that gastric acid plays an important role in preventing oral infection. Based on these results, saliva, mucosa, and gastric acid make up a natural defense, which confers high resistance to hosts against oral infection by leptospires.

Deciphering the role of ttrA and pduA genes for Salmonella enterica serovars in a chicken infection model

2021 ◽  
pp. 1-41
Author(s):  
MMS Saraiva ◽  
LB Rodrigues Alves ◽  
DFM Monte ◽  
TS Ferreira ◽  
VP Benevides ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Infection Model

scholarly journals The (Patho)Biology of SRC Kinase in Platelets and Megakaryocytes

Medicina ◽  
2020 ◽  
Vol 56 (12) ◽  
pp. 633
Author(s):  
Lore De Kock ◽  
Kathleen Freson
Keyword(s):  
Platelet Activation ◽  
Knockout Mice ◽  
Missense Variant ◽  
Surface Receptors ◽  
Src Signaling ◽  
Normal Platelet ◽  
Fibrinogen Binding ◽  
Cellular Environment ◽  
Proplatelet Formation

Proto-oncogene tyrosine-protein kinase SRC (SRC), as other members of the SRC family kinases (SFK), plays an important role in regulating signal transduction by different cell surface receptors after changes in the cellular environment. Here, we reviewed the role of SRC in platelets and megakaryocytes (MK). In platelets, inactive closed SRC is coupled to the β subunit of integrin αIIbβ3 while upon fibrinogen binding during platelet activation, αIIbβ3-mediated outside-in signaling is initiated by activation of SRC. Active open SRC now further stimulates many downstream effectors via tyrosine phosphorylation of enzymes, adaptors, and especially cytoskeletal components. Functional platelet studies using SRC knockout mice or broad spectrum SFK inhibitors pointed out that SRC mediates their spreading on fibrinogen. On the other hand, an activating pathological SRC missense variant E527K in humans that causes bleeding inhibits collagen-induced platelet activation while stimulating platelet spreading. The role of SRC in megakaryopoiesis is much less studied. SRC knockout mice have a normal platelet count though studies with SFK inhibitors point out that SRC could interfere with MK polyploidization and proplatelet formation but these inhibitors are not specific. Patients with the SRC E527K variant have thrombocytopenia due to hyperactive SRC that inhibits proplatelet formation after increased spreading of MK on fibrinogen and enhanced formation of podosomes. Studies in humans have contributed significantly to our understanding of SRC signaling in platelets and MK.

scholarly journals Induced Disruption of the Iron-Regulatory Hormone Hepcidin Inhibits Acute Inflammatory Hypoferraemia

2016 ◽  
Vol 8 (5) ◽  
pp. 517-528 ◽  
Author(s):  
Andrew E. Armitage ◽  
Pei Jin Lim ◽  
Joe N. Frost ◽  
Sant-Rayn Pasricha ◽  
Elizabeth J. Soilleux ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Brucella Abortus ◽  
Serum Iron ◽  
Vibrio Vulnificus ◽  
Iron Status ◽  
Transgenic Mouse Model ◽  
Innate Immune ◽  
Serum Hepcidin

Withdrawal of iron from serum (hypoferraemia) is a conserved innate immune antimicrobial strategy that can withhold this critical nutrient from invading pathogens, impairing their growth. Hepcidin (Hamp1) is the master regulator of iron and its expression is induced by inflammation. Mice lacking Hamp1 from birth rapidly accumulate iron and are susceptible to infection by blood-dwelling siderophilic bacteria such as Vibrio vulnificus. In order to study the innate immune role of hepcidin against a background of normal iron status, we developed a transgenic mouse model of tamoxifen-sensitive conditional Hamp1 deletion (termed iHamp1-KO mice). These mice attain adulthood with an iron status indistinguishable from littermate controls. Hamp1 disruption and the consequent decline of serum hepcidin concentrations occurred within hours of a single tamoxifen dose. We found that the TLR ligands LPS and Pam3CSK4 and heat-killed Brucella abortus caused an equivalent induction of inflammation in control and iHamp1-KO mice. Pam3CSK4 and B. abortus only caused a drop in serum iron in control mice, while hypoferraemia due to LPS was evident but substantially blunted in iHamp1-KO mice. Our results characterise a powerful new model of rapidly inducible hepcidin disruption, and demonstrate the critical contribution of hepcidin to the hypoferraemia of inflammation.

scholarly journals Role of Olfaction in the Conditioned Sucrose Preference of Sweet-Ageusic T1R3 Knockout Mice

2009 ◽  
Vol 34 (8) ◽  
pp. 685-694 ◽  
Author(s):  
S. Zukerman ◽  
K. Touzani ◽  
R. F. Margolskee ◽  
A. Sclafani
Keyword(s):  
Knockout Mice ◽  
Sucrose Preference

scholarly journals TLR4-dependent GM-CSF protects against lung injury in Gram-negative bacterial pneumonia

2012 ◽  
Vol 302 (5) ◽  
pp. L447-L454 ◽  
Author(s):  
Louis R. Standiford ◽  
Theodore J. Standiford ◽  
Michael J. Newstead ◽  
Xianying Zeng ◽  
Megan N. Ballinger ◽  
...  
Keyword(s):  
Lung Injury ◽  
Bacterial Pneumonia ◽  
Lavage Fluid ◽  
Alveolar Epithelial Cells ◽  
Intratracheal Administration ◽  
Bacterial Colony ◽  
Gram Negative ◽  
Gm Csf

Toll-like receptors (TLRs) are required for protective host defense against bacterial pathogens. However, the role of TLRs in regulating lung injury during Gram-negative bacterial pneumonia has not been thoroughly investigated. In this study, experiments were performed to evaluate the role of TLR4 in pulmonary responses against Klebsiella pneumoniae (Kp). Compared with wild-type (WT) (Balb/c) mice, mice with defective TLR4 signaling (TLR4lps-d mice) had substantially higher lung bacterial colony-forming units after intratracheal challenge with Kp, which was associated with considerably greater lung permeability and lung cell death. Reduced expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA and protein was noted in lungs and bronchoalveolar lavage fluid of TLR4 mutant mice postintratracheal Kp compared with WT mice, and primary alveolar epithelial cells (AEC) harvested from TLR4lps-d mice produced significantly less GM-CSF in vitro in response to heat-killed Kp compared with WT AEC. TLR4lps-d AEC underwent significantly more apoptosis in response to heat-killed Kp in vitro, and treatment with GM-CSF protected these cells from apoptosis in response to Kp. Finally, intratracheal administration of GM-CSF in TLR4lps-d mice significantly decreased albumin leak, lung cell apoptosis, and bacteremia in Kp-infected mice. Based on these observations, we conclude that TLR4 plays a protective role on lung epithelium during Gram-negative bacterial pneumonia, an effect that is partially mediated by GM-CSF.

scholarly journals Two Enteropathogenic Escherichia coli Type III Secreted Proteins, EspA and EspB, Are Virulence Factors

1998 ◽  
Vol 188 (10) ◽  
pp. 1907-1916 ◽  
Author(s):  
Akio Abe ◽  
Ursula Heczko ◽  
Richard G. Hegele ◽  
B. Brett Finlay
Keyword(s):  
Escherichia Coli ◽  
Virulence Factors ◽  
Enterohemorrhagic Escherichia Coli ◽  
Laser Scanning Microscopy ◽  
Secreted Proteins ◽  
Confocal Laser ◽  
Infection Model ◽  
Enteropathogenic Escherichia Coli ◽  
Type Iii

Enteropathogenic Escherichia coli (EPEC) belongs to a family of related bacterial pathogens, including enterohemorrhagic Escherichia coli (EHEC) O157:H7 and other human and animal diarrheagenic pathogens that form attaching and effacing (A/E) lesions on host epithelial surfaces. Bacterial secreted Esp proteins and a type III secretion system are conserved among these pathogens and trigger host cell signal transduction pathways and cytoskeletal rearrangements, and mediate intimate bacterial adherence to epithelial cell surfaces in vitro. However, their role in pathogenesis is still unclear. To investigate the role of Esp proteins in disease, mutations in espA and espB were constructed in rabbit EPEC serotype O103 and infection characteristics were compared to that of the wild-type strain using histology, scanning and transmission electron microscopy, and confocal laser scanning microscopy in a weaned rabbit infection model. The virulence of EspA and EspB mutant strains was severely attenuated. Additionally, neither mutant strain formed A/E lesions, nor did either one cause cytoskeletal actin rearrangements beneath the attached bacteria in the rabbit intestine. Collectively, this study shows for the first time that the type III secreted proteins EspA and EspB are needed to form A/E lesions in vivo and are indeed virulence factors. It also confirms the role of A/E lesions in disease processes.

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