scholarly journals Dexamethasone-Induced Cytokine Changes Associated with Diminished Disease Severity in Horses Infected with Anaplasma phagocytophilum

2011 ◽  
Vol 18 (11) ◽  
pp. 1962-1968 ◽  
Author(s):  
R. S. Davies ◽  
J. E. Madigan ◽  
E. Hodzic ◽  
D. L Borjesson ◽  
J. S. Dumler
Keyword(s):  
Disease Severity ◽  
Anaplasma Phagocytophilum ◽  
Macrophage Activation ◽  
Clinical Signs ◽  
Proinflammatory Response ◽  
Content Type ◽  
Granulocytic Anaplasmosis ◽  
Limb Edema ◽  
Ifn Γ ◽  
Dexamethasone Suppression

ABSTRACTAnaplasma phagocytophilumis the zoonotic cause of granulocytic anaplasmosis. We hypothesized that immune response, specifically gamma interferon (IFN-γ), plays a role in disease severity. To test this, horses were infected andIFNGexpression was pharmacologically downregulated using corticosteroids. Eight horses were infected withA. phagocytophilum; 4 received dexamethasone on days 4 to 8 of infection. Clinical signs, hematologic parameters, and transcription of cytokine/chemokine genes were compared among treated and untreated horses. Infection was quantitated bymsp2real-time PCR and microscopy. As anticipated, there was significantly greater leukopenia, thrombocytopenia, and anemia in infected versus uninfected horses. TheA. phagocytophilumload was higher for dexamethasone-treated horses. Dexamethasone reducedIFNGtranscription by day 12 andIL-8andIL-18by days 7 to 9 and increasedIL-4on day 7. The ratio ofIL-10toIFNGwas increased by dexamethasone on day 9. There were no hematologic differences between the infected horses. Dexamethasone suppression of proinflammatory response resulted in delayed infection-induced limb edema and decreased icterus, anorexia, and reluctance to move between days 6 and 9 and lower fever on day 7. These results underscore the utility of the equine model of granulocytic anaplasmosis and suggest that Th1 proinflammatory response plays a role in worsening disease severity and that disease severity can be decreased by modulating proinflammatory response. A role for Th1 response and macrophage activation in hematologic derangements elicited byA. phagocytophilumis not supported by these data and remains unproven.

scholarly journals Brucella canis Is an Intracellular Pathogen That Induces a Lower Proinflammatory Response than Smooth Zoonotic Counterparts

2015 ◽  
Vol 83 (12) ◽  
pp. 4861-4870 ◽  
Author(s):  
Carlos Chacón-Díaz ◽  
Pamela Altamirano-Silva ◽  
Gabriela González-Espinoza ◽  
María-Concepción Medina ◽  
Alejandro Alfaro-Alarcón ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Clinical Signs ◽  
Intracellular Pathogen ◽  
Virulence Determinants ◽  
Proinflammatory Response ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Type Iv ◽  
Brucella Canis ◽  
Zoonotic Risk

Canine brucellosis caused byBrucella canisis a disease of dogs and a zoonotic risk.B. canisharbors most of the virulence determinants defined for the genus, but its pathogenic strategy remains unclear since it has not been demonstrated that this natural rough bacterium is an intracellular pathogen. Studies ofB. canisoutbreaks in kennel facilities indicated that infected dogs displaying clinical signs did not present hematological alterations. A virulentB. canisstrain isolated from those outbreaks readily replicated in different organs of mice for a protracted period. However, the levels of tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-12 in serum were close to background levels. Furthermore,B. canisinduced lower levels of gamma interferon, less inflammation of the spleen, and a reduced number of granulomas in the liver in mice than didB. abortus. When the interaction ofB. caniswith cells was studiedex vivo, two patterns were observed, a predominant scattered cell-associated pattern of nonviable bacteria and an infrequent intracellular replicative pattern of viable bacteria in a perinuclear location. The second pattern, responsible for the increase in intracellular multiplication, was dependent on the type IV secretion system VirB and was seen only if the inoculum used for cell infections was in early exponential phase. Intracellular replicativeB. canisfollowed an intracellular trafficking route undistinguishable from that ofB. abortus. AlthoughB. canisinduces a lower proinflammatory response and has a stealthier replication cycle, it still displays the pathogenic properties of the genus and the ability to persist in infected organs based on the ability to multiply intracellularly.

scholarly journals Anaplasma phagocytophilum Infects Mast Cells via α1,3-Fucosylated but Not Sialylated Glycans and Inhibits IgE-Mediated Cytokine Production and Histamine Release

2011 ◽  
Vol 79 (7) ◽  
pp. 2717-2726 ◽  
Author(s):  
Nore Ojogun ◽  
Brian Barnstein ◽  
Bernice Huang ◽  
Carole A. Oskeritzian ◽  
Jonathon W. Homeister ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Anaplasma Phagocytophilum ◽  
Defense Mechanisms ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Murine Bone Marrow ◽  
Granulocytic Anaplasmosis

ABSTRACTMast cells are sentinels for infection. Upon exposure to pathogens, they release their stores of proinflammatory cytokines, chemokines, and histamine. Mast cells are also important for the control of certain tick-borne infections.Anaplasma phagocytophilumis an obligate intracellular tick-transmitted bacterium that infects neutrophils to cause the emerging disease granulocytic anaplasmosis.A. phagocytophilumadhesion to and infection of neutrophils depend on sialylated and α1,3-fucosylated glycans. We investigated the hypotheses thatA. phagocytophiluminvades mast cells and inhibits mast cell activation. We demonstrate thatA. phagocytophilumbinds and/or infects murine bone marrow-derived mast cells (BMMCs), murine peritoneal mast cells, and human skin-derived mast cells.A. phagocytophiluminfection of BMMCs depends on α1,3-fucosylated, but not sialylated, glycans.A. phagocytophilumbinding to and invasion of BMMCs do not elicit proinflammatory cytokine secretion. Moreover,A. phagocytophilum-infected cells are inhibited in the release of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-13, and histamine following stimulation with IgE or antigen. Thus,A. phagocytophilummitigates mast cell activation. These findings potentially represent a novel means by whichA. phagocytophilumusurps host defense mechanisms and shed light on the interplay between mast cells and vector-borne bacterial pathogens.

scholarly journals Anaplasma phagocytophilum Dihydrolipoamide Dehydrogenase 1 Affects Host-Derived Immunopathology during Microbial Colonization

2012 ◽  
Vol 80 (9) ◽  
pp. 3194-3205 ◽  
Author(s):  
Gang Chen ◽  
Maiara S. Severo ◽  
Olivia S. Sakhon ◽  
Anthony Choy ◽  
Michael J. Herron ◽  
...  
Keyword(s):  
Anaplasma Phagocytophilum ◽  
Extramedullary Hematopoiesis ◽  
Microbial Colonization ◽  
Dihydrolipoamide Dehydrogenase ◽  
Disease Etiology ◽  
Content Type ◽  
Granulocytic Anaplasmosis ◽  
Transposon Insertion ◽  
Pathogen Load ◽  
Mammalian Infection

ABSTRACTAnaplasma phagocytophilumis a tick-borne rickettsial pathogen that provokes an acute inflammatory response during mammalian infection. The illness caused byA. phagocytophilum, human granulocytic anaplasmosis, occurs irrespective of pathogen load and results instead from host-derived immunopathology. Thus, characterizingA. phagocytophilumgenes that affect the inflammatory process is critical for understanding disease etiology. By using anA. phagocytophilumHimar1 transposon mutant library, we showed that a single transposon insertion into theA. phagocytophilumdihydrolipoamide dehydrogenase 1 gene (lpda1[APH_0065]) affects inflammation during infection.A. phagocytophilumlackinglpda1revealed enlargement of the spleen, increased splenic extramedullary hematopoiesis, and altered clinicopathological abnormalities during mammalian colonization. Furthermore, LPDA1-derived immunopathology was independent of neutrophil infection and correlated with enhanced reactive oxygen species from NADPH oxidase and nuclear factor (NF)-κB signaling in macrophages. Taken together, these findings suggest the presence of different signaling pathways in neutrophils and macrophages duringA. phagocytophiluminvasion and highlight the importance of LPDA1 as an immunopathological molecule.

scholarly journals Adrenal Steroids Modulate the Immune Response during Brucella abortus Infection by a Mechanism That Depends on the Regulation of Cytokine Production

2015 ◽  
Vol 83 (5) ◽  
pp. 1973-1982 ◽  
Author(s):  
María Virginia Gentilini ◽  
Lis Noelia Velásquez ◽  
Paula Barrionuevo ◽  
Paula Constanza Arriola Benitez ◽  
Guillermo Hernán Giambartolomei ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Signs ◽  
Human Brucellosis ◽  
Adrenal Steroids ◽  
Class I Mhc ◽  
Mhc I ◽  
Content Type ◽  
Mhc Ii ◽  
Ifn Γ ◽  
Dhea Treatment

Human brucellosis is a protean disease with a diversity of clinical signs and symptoms resulting from infection withBrucellaspecies. Recent reports suggest a cross-regulation between adrenal steroids (cortisol and dehydroepiandrosterone [DHEA]) and the immune system. Monocytes and macrophages are the main replication niche forBrucella. Therefore, we investigated the role of adrenal hormones on the modulation of the immune response mediated by macrophages inB. abortusinfection. Cortisol treatment duringB. abortusinfection significantly inhibits cytokine, chemokine, and MMP-9 secretion. In contrast, DHEA treatment had no effect. However, DHEA treatment increases the expression of costimulatory molecules (CD40, CD86), the adhesion molecule CD54, and major histocompatibility complex class I (MHC-I) and MHC-II expression on the surface ofB. abortus-infected monocytes. It is known thatB. abortusinfection inhibits MHC-I and MHC-II expression induced by gamma interferon (IFN-γ) treatment. DHEA reversesB. abortusdownmodulation of the MHC-I and -II expression induced by IFN-γ. Taken together, our data indicate that DHEA immune intervention may positively affect monocyte activity duringB. abortusinfection.

Anaplasma phagocytophilum in domestic cats from Germany, Austria and Switzerland and clinical/laboratory findings in 18 PCR-positive cats (2008–2020)

2021 ◽  
pp. 1098612X2110174
Author(s):  
Ingo Schäfer ◽  
Barbara Kohn ◽  
Elisabeth Müller
Keyword(s):  
Anaplasma Phagocytophilum ◽  
Clinical Laboratory ◽  
Case Reports ◽  
Clinical Signs ◽  
Indirect Detection ◽  
Detection Methods ◽  
Direct Pcr ◽  
Laboratory Findings ◽  
Additional Information ◽  
Granulocytic Anaplasmosis

Objectives Anaplasma phagocytophilum is considered the most significant rickettsial pathogen affecting cats. The organism is transmitted by ticks of the species Ixodes ricinus in Central Europe and can cause granulocytic anaplasmosis in pets, wildlife and humans. The aims of this study were to assess the frequency of positive test results for A phagocytophilum in cats in Germany, Austria and Switzerland, as well as to evaluate clinical and laboratory findings in cats with positive PCR results. Methods This study included the results of direct (PCR) and indirect detection methods (immunofluorescence antibody tests [IFAT]) requested by veterinarians in Germany, Austria and Switzerland between 2008 and 2020 from the LABOKLIN laboratory (Bad Kissingen, Germany). The veterinarians treating the PCR-positive cats were contacted by telephone to enquire about their clinical signs, laboratory findings, management and outcomes. Results In total, 244/1636 cats (15%) tested positive by direct (PCR: n = 27/725 [4%]) and/or indirect detection methods (IFAT: n = 221/956 [23%]). In 18/26 cats with PCR results positive for A phagocytophilum, additional information about clinical signs, laboratory findings, treatment and outcome was obtained. Of these 18 cats, five had comorbidities independent of their infection with A phagocytophilum. The most common clinical signs in PCR-positive cats (total/without comorbidities) were lethargy (83%/92%), fever (83%/85%) and thrombocytopenia (61%/62%). Overall, more than half (57%) of the cats with and without comorbidities recovered clinically. Conclusions and relevance Infections with A phagocytophilum should be considered as differential diagnoses in cats with tick infestation, lethargy, fever and thrombocytopenia. The clinical signs and laboratory findings are consistent with published case reports in cats. Ectoparasite prophylaxis in cats is recommended throughout the entire year.

scholarly journals Complex T Cell Interactions Contribute to Helicobacter pylori Gastritis in Mice

2012 ◽  
Vol 81 (3) ◽  
pp. 740-752 ◽  
Author(s):  
Brian M. Gray ◽  
Clinton A. Fontaine ◽  
Sara A. Poe ◽  
Kathryn A. Eaton
Keyword(s):  
T Cells ◽  
Helicobacter Pylori ◽  
T Cell ◽  
Published Data ◽  
Proinflammatory Response ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Ifn Γ ◽  
H Pylori

ABSTRACTDisease due to the gastric pathogenHelicobacter pylorivaries in severity from asymptomatic to peptic ulcer disease and cancer. Accumulating evidence suggests that one source of this variation is an abnormal host response. The goal of this study was to use a mouse model ofH. pylorigastritis to investigate the roles of regulatory T cells (Treg) as well as proinflammatory T cells (Th1 and Th17) in gastritis, gastric T cell engraftment, and gastric cytokine production. Our results support published data indicating that severe gastritis in T cell recipient mice is due to failure of Treg engraftment, that Treg ameliorate gastritis, and that the proinflammatory response is attributable to interactions between several cell subsets and cytokines. We confirmed that gamma interferon (IFN-γ) is essential for induction of gastritis but showed that IFN-γ-producing CD4 T cells are not necessary. Interleukin 17A (IL-17A) also contributed to gastritis, but to a lesser extent than IFN-γ. Tumor necrosis factor alpha (TNF-α) and IL-17F were also elevated in association with disease. These results indicate that whileH. pylori-specific CD4+T cells and IFN-γ are both essential for induction of gastritis due toH. pylori, IFN-γ production by T cells is not essential. It is likely that other proinflammatory cytokines, such as IL-17F and TNF-α, shown to be elevated in this model, also contribute to the induction of disease. We suggest that gastritis due toH. pyloriis associated with loss of immunoregulation and alteration of several cytokines and cell subsets and cannot be attributed to a single immune pathway.

scholarly journals Impairment of Gamma Interferon Signaling in Human Neutrophils Infected with Anaplasma phagocytophilum

2009 ◽  
Vol 78 (1) ◽  
pp. 358-363 ◽  
Author(s):  
Uta Bussmeyer ◽  
Arup Sarkar ◽  
Kirsten Broszat ◽  
Tanja Lüdemann ◽  
Sonja Möller ◽  
...  
Keyword(s):  
Anaplasma Phagocytophilum ◽  
Gamma Interferon ◽  
Polymorphonuclear Neutrophil ◽  
Human Neutrophils ◽  
Neutrophil Granulocytes ◽  
Interferon Signaling ◽  
Granulocytic Anaplasmosis ◽  
Infected Cells ◽  
Ifn Γ

ABSTRACT Anaplasma phagocytophilum, the causative agent of tick-borne human granulocytic anaplasmosis (HGA), is an intracellular bacterium which survives and multiplies inside polymorphonuclear neutrophil granulocytes (PMN). Increased bacterial burden in gamma interferon (IFN-γ)-deficient mice suggested a major role of IFN-γ in the control of A. phagocytophilum. Here we investigated whether infection of human PMN with A. phagocytophilum impairs IFN-γ signaling thus facilitating intracellular survival of the bacterium. The secretion of the IFN-γ-inducible chemokines IP-10/CXCL10 and MIG/CXCL9 was markedly inhibited in infected neutrophils. Molecular analyses revealed that, compared to uninfected PMN, A. phagocytophilum decreased the expression of the IFN-γ receptor α-chain CD119, diminished the IFN-γ-induced phosphorylation of STAT1, and enhanced the expression of SOCS1 and SOCS3 in PMN. Since IFN-γ activates various antibacterial effector mechanisms of PMN, the impaired IFN-γ signaling in infected cells likely contributes to the survival of A. phagocytophilum inside PMN and to HGA disease development.

scholarly journals Neither Classical nor Alternative Macrophage Activation Is Required for Pneumocystis Clearance during Immune Reconstitution Inflammatory Syndrome

2015 ◽  
Vol 83 (12) ◽  
pp. 4594-4603 ◽  
Author(s):  
Zhuo-Qian Zhang ◽  
Jing Wang ◽  
Zachary Hoy ◽  
Achsah Keegan ◽  
Samir Bhagwat ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Macrophage Activation ◽  
Macrophage Polarization ◽  
Severe Disease ◽  
Interleukin 4 ◽  
Content Type ◽  
Ifn Γ ◽  
Inflammatory Syndrome

Pneumocystisis a respiratory fungal pathogen that causes pneumonia (Pneumocystispneumonia [PcP]) in immunocompromised patients. Alveolar macrophages are critical effectors for CD4+T cell-dependent clearance ofPneumocystis, and previous studies found that alternative macrophage activation accelerates fungal clearance during PcP-related immune reconstitution inflammatory syndrome (IRIS). However, the requirement for either classically or alternatively activated macrophages forPneumocystisclearance has not been determined. Therefore, RAG2−/−mice lacking either the interferon gamma (IFN-γ) receptor (IFN-γR) or interleukin 4 receptor alpha (IL-4Rα) were infected withPneumocystis. These mice were then immune reconstituted with wild-type lymphocytes to preserve the normal T helper response while preventing downstream effects of Th1 or Th2 effector cytokines on macrophage polarization. As expected, RAG2−/−mice developed severe disease but effectively clearedPneumocystisand resolved IRIS. Neither RAG/IFN-γR−/−nor RAG/IL-4Rα−/−mice displayed impairedPneumocystisclearance. However, RAG/IFN-γR−/−mice developed a dysregulated immune response, with exacerbated IRIS and greater pulmonary function deficits than those in RAG2 and RAG/IL-4Rα−/−mice. RAG/IFN-γR−/−mice had elevated numbers of lung CD4+T cells, neutrophils, eosinophils, and NK cells but severely depressed numbers of lung CD8+T suppressor cells. Impaired lung CD8+T cell responses in RAG/IFN-γR−/−mice were associated with elevated lung IFN-γ levels, and neutralization of IFN-γ restored the CD8 response. These data demonstrate that restricting the ability of macrophages to polarize in response to Th1 or Th2 cytokines does not impairPneumocystisclearance. However, a cell type-specific IFN-γ/IFN-γR-dependent mechanism regulates CD8+T suppressor cell recruitment, limits immunopathogenesis, preserves lung function, and enhances the resolution of PcP-related IRIS.

scholarly journals Expression and Immunogenicity of Recombinant Immunoreactive Surface Protein 2 of Anaplasma phagocytophilum

2012 ◽  
Vol 19 (6) ◽  
pp. 919-923 ◽  
Author(s):  
Qiang Yu ◽  
Chuang-fu Chen ◽  
Qiang Chen ◽  
Li-juan Zhang
Keyword(s):  
Recombinant Protein ◽  
Anaplasma Phagocytophilum ◽  
Surface Protein ◽  
Immunofluorescence Assay ◽  
Enzyme Linked Immunosorbent Assay ◽  
Content Type ◽  
Major Surface Protein ◽  
Granulocytic Anaplasmosis ◽  
Major Surface ◽  
Diagnostic Reagent

ABSTRACTHuman granulocytic anaplasmosis (HGA), caused byAnaplasma phagocytophilum, is an emerging tick-borne zoonotic disease throughout the world. The first HGA cases in China were documented in 2008, and the greatest challenge posed by the disease is rapid and accurate diagnosis during the acute phage of illness. In this study, we successfully cloned and expressed anA. phagocytophilumimmunoreactive surface protein (major surface protein 2 [MSP2]) and demonstrated that this recombinant protein has natural immunogenicity by Western blotting and enzyme-linked immunosorbent assay (ELISA) using human HGA-positive sera and reference rabbit HGA-positive sera. The rabbit antisera against the recombinant protein also reacted actively with the natural antigen ofA. phagocytophilumby immunofluorescence assay (IFA). No cross-reaction was observed between the recombinant protein and rabbit antisera against 10 common members of the orderRickettsialesby ELISA when the sera were diluted more than 1:100. We concluded that the recombinant MSP2 protein exhibited excellent antigenicity and specificity, results that should lay the foundation for the development of a simple and rapid diagnostic reagent and a vaccination for anaplasmosis.

scholarly journals Epidemiological and Clinicopathological Features of Anaplasma phagocytophilum Infection in Dogs: A Systematic Review

2021 ◽  
Vol 8 ◽  
Author(s):  
Sarah El Hamiani Khatat ◽  
Sylvie Daminet ◽  
Luc Duchateau ◽  
Latifa Elhachimi ◽  
Malika Kachani ◽  
...  
Keyword(s):  
Anaplasma Phagocytophilum ◽  
Clinical Signs ◽  
Febrile Illness ◽  
Positive Association ◽  
Response To Treatment ◽  
Host Immune System ◽  
Granulocytic Anaplasmosis ◽  
The Usa ◽  
Vector Borne

Anaplasma phagocytophilum is a worldwide emerging zoonotic tick-borne pathogen transmitted by Ixodid ticks and naturally maintained in complex and incompletely assessed enzootic cycles. Several studies have demonstrated an extensive genetic variability with variable host tropisms and pathogenicity. However, the relationship between genetic diversity and modified pathogenicity is not yet understood. Because of their proximity to humans, dogs are potential sentinels for the transmission of vector-borne pathogens. Furthermore, the strong molecular similarity between human and canine isolates of A. phagocytophilum in Europe and the USA and the positive association in the distribution of human and canine cases in the USA emphasizes the epidemiological role of dogs. Anaplasma phagocytophilum infects and survives within neutrophils by disregulating neutrophil functions and evading specific immune responses. Moreover, the complex interaction between the bacterium and the infected host immune system contribute to induce inflammatory injuries. Canine granulocytic anaplasmosis is an acute febrile illness characterized by lethargy, inappetence, weight loss and musculoskeletal pain. Hematological and biochemistry profile modifications associated with this disease are unspecific and include thrombocytopenia, anemia, morulae within neutrophils and increased liver enzymes activity. Coinfections with other tick-borne pathogens (TBPs) may occur, especially with Borrelia burgdorferi, complicating the clinical presentation, diagnosis and response to treatment. Although clinical studies have been published in dogs, it remains unclear if several clinical signs and clinicopathological abnormalities can be related to this infection.

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