Experimental Infection of C3H/HeJ Mice with the NY18 Isolate of <i>Anaplasma phagocytophilum</i>

Blás-Machado, Uriel; Fuente, José de la; Blouin, Edmour F.; Almazán, Consuelo; Kocan, Katherine M.; Mysore, Jagannatha

doi:10.1354/vp.44-1-64

Cited by 18 publications

(16 citation statements)

References 44 publications

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“…The detection of bacterial DNA by PCR showed a prepatent period (calculated as the number of days from the time of pig inoculation with infected tick cells to the first day that blood samples were found to be A. phagocytophilum positive by PCR) of 15 days, similar to that found in sheep [64] and white-tailed deer [65] but lower than in mice [66] inoculated with A. phagocytophilum (NY-18) infected cells. At 36 dpi only two animals were PCR positive and by 47 dpi all animals were negative, suggesting duration of approximately 30 days for the primary bacteremia.…”

Section: Discussionsupporting

confidence: 63%

Gene expression profile suggests that pigs (Sus scrofa) are susceptible to Anaplasma phagocytophilum but control infection

Galindo

Ayllón

Smrdel³

et al. 2012

Parasites Vectors

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BackgroundAnaplasma phagocytophilum infects a wide variety of hosts and causes granulocytic anaplasmosis in humans, horses and dogs and tick-borne fever in ruminants. Infection with A. phagocytophilum results in the modification of host gene expression and immune response. The objective of this research was to characterize gene expression in pigs (Sus scrofa) naturally and experimentally infected with A. phagocytophilum trying to identify mechanisms that help to explain low infection prevalence in this species.ResultsFor gene expression analysis in naturally infected pigs, microarray hybridization was used. The expression of differentially expressed immune response genes was analyzed by real-time RT-PCR in naturally and experimentally infected pigs. Results suggested that A. phagocytophilum infection affected cytoskeleton rearrangement and increased both innate and adaptive immune responses by up regulation of interleukin 1 receptor accessory protein-like 1 (IL1RAPL1), T-cell receptor alpha chain (TCR-alpha), thrombospondin 4 (TSP-4) and Gap junction protein alpha 1 (GJA1) genes. Higher serum levels of IL-1 beta, IL-8 and TNF-alpha in infected pigs when compared to controls supported data obtained at the mRNA level.ConclusionsThese results suggested that pigs are susceptible to A. phagocytophilum but control infection, particularly through activation of innate immune responses, phagocytosis and autophagy. This fact may account for the low infection prevalence detected in pigs in some regions and thus their low or no impact as a reservoir host for this pathogen. These results advanced our understanding of the molecular mechanisms at the host-pathogen interface and suggested a role for newly reported genes in the protection of pigs against A. phagocytophilum.

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Section: Discussionsupporting

confidence: 63%

Gene expression profile suggests that pigs (Sus scrofa) are susceptible to Anaplasma phagocytophilum but control infection

Galindo

Ayllón

Smrdel³

et al. 2012

Parasites Vectors

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“…An examination of the literature revealed 61 publications that used the mouse model of granulocytic anaplasmosis. Of the 61 reports, 31 did not disclose the gender, 13 used only females, 9 used only males, 6 included both sexes, 1 used females for one group and males for another, and 1 used females for the experimental group but male and females for the control group [ 20 , 21 , 22 , 23 , 25 , 26 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ,…”

Section: Resultsmentioning

confidence: 99%

“…We sought to determine if such a correlation exists. Following inoculation, the A. phagocytophilum peripheral blood burden in immunocompetent wild-type mice tends to peak by day 12 and subsides thereafter to undetectable or near undetectable levels by days 21 to 28 [ 23 , 26 , 38 , 45 , 52 , 58 , 60 , 64 , 68 , 71 , 73 , 75 , 78 , 81 , 84 ]. C57Bl/6 mice are commonly used for studying A. phagocytophilum infection [ 26 , 34 , 36 , 38 , 39 , 40 , 41 , 52 , 61 , 62 , 65 , 68 , 70 , 73 , 75 , 76 , 78 , 84 , 85 ].…”

Section: Resultsmentioning

confidence: 99%

Differential Susceptibility of Male Versus Female Laboratory Mice to Anaplasma phagocytophilum Infection

et al. 2018

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Human granulocytic anaplasmosis (HGA) is a debilitating, non-specific febrile illness caused by the granulocytotropic obligate intracellular bacterium called Anaplasma phagocytophilum. Surveillance studies indicate a higher prevalence of HGA in male versus female patients. Whether this discrepancy correlates with differential susceptibility of males and females to A. phagocytophilum infection is unknown. Laboratory mice have long been used to study granulocytic anaplasmosis. Yet, sex as a biological variable (SABV) in this model has not been evaluated. In this paper, groups of male and female C57Bl/6 mice that had been infected with A. phagocytophilum were assessed for the bacterial DNA load in the peripheral blood, the percentage of neutrophils harboring bacterial inclusions called morulae, and splenomegaly. Infected male mice exhibited as much as a 1.85-fold increase in the number of infected neutrophils, which is up to a 1.88-fold increase in the A. phagocytophilum DNA load, and a significant increase in spleen size when compared to infected female mice. The propensity of male mice to develop a higher level of A. phagocytophilum infection is relevant for studies utilizing the mouse model. This stresses the importance of including SABV and aligns with the observed higher incidence of infection in male versus female patients.

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“…In this study, we have successfully infected BALB/c mice with A. marginale , similar to what have been described for Human granulocytic anaplasmosis [26], and this mouse model of anaplasmosis proved to be a valuable tool to evaluate novel immunogens prior to bovine challenges.…”

Section: Discussionmentioning

confidence: 94%

Epitope-Based Vaccines with the Anaplasma marginale MSP1a Functional Motif Induce a Balanced Humoral and Cellular Immune Response in Mice

et al. 2013

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Bovine anaplasmosis is a hemoparasitic disease that causes considerable economic loss to the dairy and beef industries. Cattle immunized with the Anaplasma marginale MSP1 outer membrane protein complex presents a protective humoral immune response; however, its efficacy is variable. Immunodominant epitopes seem to be a key-limiting factor for the adaptive immunity. We have successfully demonstrated that critical motifs of the MSP1a functional epitope are essential for antibody recognition of infected animal sera, but its protective immunity is yet to be tested. We have evaluated two synthetic vaccine formulations against A. marginale, using epitope-based approach in mice. Mice infection with bovine anaplasmosis was demonstrated by qPCR analysis of erythrocytes after 15-day exposure. A proof-of-concept was obtained in this murine model, in which peptides conjugated to bovine serum albumin were used for immunization in three 15-day intervals by intraperitoneal injections before challenging with live bacteria. Blood samples were analyzed for the presence of specific IgG2a and IgG1 antibodies, as well as for the rickettsemia analysis. A panel containing the cytokines’ transcriptional profile for innate and adaptive immune responses was carried out through qPCR. Immunized BALB/c mice challenged with A. marginale presented stable body weight, reduced number of infected erythrocytes, and no mortality; and among control groups mortality rates ranged from 15% to 29%. Additionally, vaccines have significantly induced higher IgG2a than IgG1 response, followed by increased expression of pro-inflammatory cytokines. This is a successful demonstration of epitope-based vaccines, and protection against anaplasmosis may be associated with elicitation of effector functions of humoral and cellular immune responses in murine model.

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Experimental Infection of C3H/HeJ Mice with the NY18 Isolate of Anaplasma phagocytophilum

Cited by 18 publications

References 44 publications

Gene expression profile suggests that pigs (Sus scrofa) are susceptible to Anaplasma phagocytophilum but control infection

Gene expression profile suggests that pigs (Sus scrofa) are susceptible to Anaplasma phagocytophilum but control infection

Differential Susceptibility of Male Versus Female Laboratory Mice to Anaplasma phagocytophilum Infection

Epitope-Based Vaccines with the Anaplasma marginale MSP1a Functional Motif Induce a Balanced Humoral and Cellular Immune Response in Mice

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