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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

Concentrations of serum inflammatory cytokines are increased in response to R. parkeri inoculation.Comparisons of interleukin-6 (D), interferon γ (E), and interleukin-15 (F) concentrations in serum of all animals at the various indicated time points as determined by a magnetic cytokine bead panel kit. Measurements were performed in duplicate with the bars indicating standard error. For presentation purposes all of the final time points are plotted as 31 dpi as opposed to 31, 32, and 35 dpi for the tick-only, tick feeding + R. parkeri, and R. parkeri-only groups, respectively.
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pone.0135175.g003: Concentrations of serum inflammatory cytokines are increased in response to R. parkeri inoculation.Comparisons of interleukin-6 (D), interferon γ (E), and interleukin-15 (F) concentrations in serum of all animals at the various indicated time points as determined by a magnetic cytokine bead panel kit. Measurements were performed in duplicate with the bars indicating standard error. For presentation purposes all of the final time points are plotted as 31 dpi as opposed to 31, 32, and 35 dpi for the tick-only, tick feeding + R. parkeri, and R. parkeri-only groups, respectively.

Mentions: There were 17-20-fold increases in IL-6 concentrations in both of the tick + R. parkeri macaques at 1 dpi as compared to pre-inoculation values, with moderate elevations (8-12-fold baseline concentrations) noted at 4 dpi for the same two animals and macaque #1 from the R. parkeri-only group (Fig 3A). Moderate elevations (13-fold greater than pre-inoculation values) were noted in IFNγ concentration in primate #1 from the tick + R. parkeri group at 1 dpi with mild elevations (less than 7-fold pre-inoculation data) in all R. parkeri-inoculated animals at 4 dpi (Fig 3B). Also, there were mild increases (1.7 to 2.3-fold greater than baseline) in IL-15 concentration in both animals from the tick + R. parkeri group as well as R. parkeri-only macaque #2 at 4 dpi, with mild increases (1.5-fold greater than pre-inoculation data) at 4 dpi and 11 dpi in the tick-only animal. There were no apparent differences between groups for the remainder of the cytokines evaluated. All animals inoculated with R. parkeri had anti-R. parkeri IgG titers of at least 1:256 at 11 dpi with at least a 4-fold increase in titers by 31–35 dpi (Table 1). Anti-Rickettsia IgG was not detected in the tick-only animal during the experiment, nor in any of the animals prior to inoculation.


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)

Concentrations of serum inflammatory cytokines are increased in response to R. parkeri inoculation.Comparisons of interleukin-6 (D), interferon γ (E), and interleukin-15 (F) concentrations in serum of all animals at the various indicated time points as determined by a magnetic cytokine bead panel kit. Measurements were performed in duplicate with the bars indicating standard error. For presentation purposes all of the final time points are plotted as 31 dpi as opposed to 31, 32, and 35 dpi for the tick-only, tick feeding + R. parkeri, and R. parkeri-only groups, respectively.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0135175.g003: Concentrations of serum inflammatory cytokines are increased in response to R. parkeri inoculation.Comparisons of interleukin-6 (D), interferon γ (E), and interleukin-15 (F) concentrations in serum of all animals at the various indicated time points as determined by a magnetic cytokine bead panel kit. Measurements were performed in duplicate with the bars indicating standard error. For presentation purposes all of the final time points are plotted as 31 dpi as opposed to 31, 32, and 35 dpi for the tick-only, tick feeding + R. parkeri, and R. parkeri-only groups, respectively.
Mentions: There were 17-20-fold increases in IL-6 concentrations in both of the tick + R. parkeri macaques at 1 dpi as compared to pre-inoculation values, with moderate elevations (8-12-fold baseline concentrations) noted at 4 dpi for the same two animals and macaque #1 from the R. parkeri-only group (Fig 3A). Moderate elevations (13-fold greater than pre-inoculation values) were noted in IFNγ concentration in primate #1 from the tick + R. parkeri group at 1 dpi with mild elevations (less than 7-fold pre-inoculation data) in all R. parkeri-inoculated animals at 4 dpi (Fig 3B). Also, there were mild increases (1.7 to 2.3-fold greater than baseline) in IL-15 concentration in both animals from the tick + R. parkeri group as well as R. parkeri-only macaque #2 at 4 dpi, with mild increases (1.5-fold greater than pre-inoculation data) at 4 dpi and 11 dpi in the tick-only animal. There were no apparent differences between groups for the remainder of the cytokines evaluated. All animals inoculated with R. parkeri had anti-R. parkeri IgG titers of at least 1:256 at 11 dpi with at least a 4-fold increase in titers by 31–35 dpi (Table 1). Anti-Rickettsia IgG was not detected in the tick-only animal during the experiment, nor in any of the animals prior to inoculation.

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