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Amblyomma maculatum Feeding Augments Rickettsia parkeri Infection in a Rhesus Macaque Model: A Pilot Study.

Banajee KH, Embers ME, Langohr IM, Doyle LA, Hasenkampf NR, Macaluso KR - PLoS ONE (2015)

Bottom Line: However, the effect of this immunomodulation on Rickettsia transmission and pathology in an immunocompetent vertebrate host has not been fully examined.As opposed to the tick-only animal, all Rickettsia-inoculated macaques developed inflammatory leukograms, elevated C-reactive protein concentrations, and elevated TH1 (interferon-γ, interleukin-15) and acute phase inflammatory cytokines (interleukin-6) post-inoculation, with greater neutrophilia and interleukin-6 concentrations in the tick plus R. parkeri group.Furthermore, dissemination of R. parkeri to draining lymph nodes early in infection and increased persistence at the inoculation site were observed in the tick plus R. parkeri group.

View Article: PubMed Central - PubMed

Affiliation: Vector-borne Disease Laboratories, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, 70803, United States of America.

ABSTRACT
Rickettsia parkeri is an emerging eschar-causing human pathogen in the spotted fever group of Rickettsia and is transmitted by the Gulf coast tick, Amblyomma maculatum. Tick saliva has been shown to alter both the cellular and humoral components of the innate and adaptive immune systems. However, the effect of this immunomodulation on Rickettsia transmission and pathology in an immunocompetent vertebrate host has not been fully examined. We hypothesize that, by modifying the host immune response, tick feeding enhances infection and pathology of pathogenic spotted fever group Rickettsia sp. In order to assess this interaction in vivo, a pilot study was conducted using five rhesus macaques that were divided into three groups. One group was intradermally inoculated with low passage R. parkeri (Portsmouth strain) alone (n = 2) and another group was inoculated during infestation by adult, R. parkeri-free A. maculatum (n = 2). The final macaque was infested with ticks alone (tick feeding control group). Blood, lymph node and skin biopsies were collected at several time points post-inoculation/infestation to assess pathology and quantify rickettsial DNA. As opposed to the tick-only animal, all Rickettsia-inoculated macaques developed inflammatory leukograms, elevated C-reactive protein concentrations, and elevated TH1 (interferon-γ, interleukin-15) and acute phase inflammatory cytokines (interleukin-6) post-inoculation, with greater neutrophilia and interleukin-6 concentrations in the tick plus R. parkeri group. While eschars formed at all R. parkeri inoculation sites, larger and slower healing eschars were observed in the tick feeding plus R. parkeri group. Furthermore, dissemination of R. parkeri to draining lymph nodes early in infection and increased persistence at the inoculation site were observed in the tick plus R. parkeri group. This study indicates that rhesus macaques can be used to model R. parkeri rickettsiosis, and suggests that immunomodulatory factors introduced during tick feeding may enhance the pathogenicity of spotted fever group Rickettsia.

No MeSH data available.


Related in: MedlinePlus

Experimental design for tick feeding, R. parkeri/Vero cell inoculation, and sample collection.Adult Amblyomma maculatum ticks were placed on the hosts as indicated. Either a partially purified low passage human isolate of R. parkeri or an uninfected Vero cell inoculum was administered at the indicated time points. Blood collection, physical exams (PE), rectal temperatures, and skin and lymph node biopsies were taken from all animals at the indicated time points. Complete necropsies were performed at the end of the study as indicated.
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pone.0135175.g001: Experimental design for tick feeding, R. parkeri/Vero cell inoculation, and sample collection.Adult Amblyomma maculatum ticks were placed on the hosts as indicated. Either a partially purified low passage human isolate of R. parkeri or an uninfected Vero cell inoculum was administered at the indicated time points. Blood collection, physical exams (PE), rectal temperatures, and skin and lymph node biopsies were taken from all animals at the indicated time points. Complete necropsies were performed at the end of the study as indicated.

Mentions: The macaques were split into three groups as outlined in Fig 1. Two animals each were placed in the R. parkeri-only and the tick + R. parkeri groups, and one was placed in the tick-only group. All animals were shaved and fitted with primate jackets (Lomir Biomedical, Inc., Notre-Dame-de-l’Île-Perrot, QC, Canada) one week prior to tick infestation to allow the primates to become acclimated to them. The tick exposure groups were infested with five male and ten female adult ticks using a tick containment device as previously described [38]. The number of ticks was chosen based on the fact that they could comfortably feed and engorge in the space allowed within the containment device. Male ticks were placed on the host and allowed to attach one day after applying the tick containment device, followed by female tick infestation two days later to stimulate the production of pheromones secreted during male feeding, such as the attraction-aggregation-attachment pheromone, which facilitate female tick attachment and feeding [39]. The tick feeding sites and containment devices were assessed, cleaned, and reinforced as needed at 3, 7, and 12 days post female tick infestation. All of the animals were inoculated intradermally 13 days after jacket placement (3 days after female tick infestation for the tick groups) with three 200 μL injections of either partially purified Vero cell lysate or R. parkeri at the tick feeding site for the tick groups or at a similar location on the cranial back for the R. parkeri-only group. Ticks, containment devices, and jackets were removed 12 days after female tick infestation.


Amblyomma maculatum Feeding Augments Rickettsia parkeri Infection in a Rhesus Macaque Model: A Pilot Study.

Banajee KH, Embers ME, Langohr IM, Doyle LA, Hasenkampf NR, Macaluso KR - PLoS ONE (2015)

Experimental design for tick feeding, R. parkeri/Vero cell inoculation, and sample collection.Adult Amblyomma maculatum ticks were placed on the hosts as indicated. Either a partially purified low passage human isolate of R. parkeri or an uninfected Vero cell inoculum was administered at the indicated time points. Blood collection, physical exams (PE), rectal temperatures, and skin and lymph node biopsies were taken from all animals at the indicated time points. Complete necropsies were performed at the end of the study as indicated.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526656&req=5

pone.0135175.g001: Experimental design for tick feeding, R. parkeri/Vero cell inoculation, and sample collection.Adult Amblyomma maculatum ticks were placed on the hosts as indicated. Either a partially purified low passage human isolate of R. parkeri or an uninfected Vero cell inoculum was administered at the indicated time points. Blood collection, physical exams (PE), rectal temperatures, and skin and lymph node biopsies were taken from all animals at the indicated time points. Complete necropsies were performed at the end of the study as indicated.
Mentions: The macaques were split into three groups as outlined in Fig 1. Two animals each were placed in the R. parkeri-only and the tick + R. parkeri groups, and one was placed in the tick-only group. All animals were shaved and fitted with primate jackets (Lomir Biomedical, Inc., Notre-Dame-de-l’Île-Perrot, QC, Canada) one week prior to tick infestation to allow the primates to become acclimated to them. The tick exposure groups were infested with five male and ten female adult ticks using a tick containment device as previously described [38]. The number of ticks was chosen based on the fact that they could comfortably feed and engorge in the space allowed within the containment device. Male ticks were placed on the host and allowed to attach one day after applying the tick containment device, followed by female tick infestation two days later to stimulate the production of pheromones secreted during male feeding, such as the attraction-aggregation-attachment pheromone, which facilitate female tick attachment and feeding [39]. The tick feeding sites and containment devices were assessed, cleaned, and reinforced as needed at 3, 7, and 12 days post female tick infestation. All of the animals were inoculated intradermally 13 days after jacket placement (3 days after female tick infestation for the tick groups) with three 200 μL injections of either partially purified Vero cell lysate or R. parkeri at the tick feeding site for the tick groups or at a similar location on the cranial back for the R. parkeri-only group. Ticks, containment devices, and jackets were removed 12 days after female tick infestation.

Bottom Line: However, the effect of this immunomodulation on Rickettsia transmission and pathology in an immunocompetent vertebrate host has not been fully examined.As opposed to the tick-only animal, all Rickettsia-inoculated macaques developed inflammatory leukograms, elevated C-reactive protein concentrations, and elevated TH1 (interferon-γ, interleukin-15) and acute phase inflammatory cytokines (interleukin-6) post-inoculation, with greater neutrophilia and interleukin-6 concentrations in the tick plus R. parkeri group.Furthermore, dissemination of R. parkeri to draining lymph nodes early in infection and increased persistence at the inoculation site were observed in the tick plus R. parkeri group.

View Article: PubMed Central - PubMed

Affiliation: Vector-borne Disease Laboratories, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, 70803, United States of America.

ABSTRACT
Rickettsia parkeri is an emerging eschar-causing human pathogen in the spotted fever group of Rickettsia and is transmitted by the Gulf coast tick, Amblyomma maculatum. Tick saliva has been shown to alter both the cellular and humoral components of the innate and adaptive immune systems. However, the effect of this immunomodulation on Rickettsia transmission and pathology in an immunocompetent vertebrate host has not been fully examined. We hypothesize that, by modifying the host immune response, tick feeding enhances infection and pathology of pathogenic spotted fever group Rickettsia sp. In order to assess this interaction in vivo, a pilot study was conducted using five rhesus macaques that were divided into three groups. One group was intradermally inoculated with low passage R. parkeri (Portsmouth strain) alone (n = 2) and another group was inoculated during infestation by adult, R. parkeri-free A. maculatum (n = 2). The final macaque was infested with ticks alone (tick feeding control group). Blood, lymph node and skin biopsies were collected at several time points post-inoculation/infestation to assess pathology and quantify rickettsial DNA. As opposed to the tick-only animal, all Rickettsia-inoculated macaques developed inflammatory leukograms, elevated C-reactive protein concentrations, and elevated TH1 (interferon-γ, interleukin-15) and acute phase inflammatory cytokines (interleukin-6) post-inoculation, with greater neutrophilia and interleukin-6 concentrations in the tick plus R. parkeri group. While eschars formed at all R. parkeri inoculation sites, larger and slower healing eschars were observed in the tick feeding plus R. parkeri group. Furthermore, dissemination of R. parkeri to draining lymph nodes early in infection and increased persistence at the inoculation site were observed in the tick plus R. parkeri group. This study indicates that rhesus macaques can be used to model R. parkeri rickettsiosis, and suggests that immunomodulatory factors introduced during tick feeding may enhance the pathogenicity of spotted fever group Rickettsia.

No MeSH data available.


Related in: MedlinePlus