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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

Evidence of an acute phase inflammatory response in response to R. parkeri inoculation.Comparisons of neutrophil (A), lymphocyte (B), and C-reactive protein (C) concentrations in peripheral blood of all animals at the various time points indicated. Neutrophilia, lymphopenia, and elevated C-reactive protein were noted in the acute phase of infection after R. parkeri inoculation with greater neutrophilia noted in the tick + R. parkeri group. 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.g002: Evidence of an acute phase inflammatory response in response to R. parkeri inoculation.Comparisons of neutrophil (A), lymphocyte (B), and C-reactive protein (C) concentrations in peripheral blood of all animals at the various time points indicated. Neutrophilia, lymphopenia, and elevated C-reactive protein were noted in the acute phase of infection after R. parkeri inoculation with greater neutrophilia noted in the tick + R. parkeri group. 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: No differences in weight or temperature were noted between treatment groups during the study. Mild to marked peripheral lymphadenopathy was noted in all animals from 4 dpi to 11 dpi primarily affecting the axillary lymph nodes. At 1 dpi, moderate neutrophilia (greater than 4-fold pre-inoculation values) was noted in both primates in the tick + R. parkeri group as compared to mild neutrophilia (less than 3-fold baseline concentrations) in both R. parkeri-only primates (Fig 2A). All of these animals had mild neutrophilia at 4 dpi that resolved by the time of necropsy in all animals except for macaque #1 in the tick + R. parkeri group. The tick-only macaque developed mild neutrophilia at 4 dpi (less than 3-fold pre-inoculation levels), with values returning to baseline at necropsy. All of the animals inoculated with R. parkeri were lymphopenic at 1 and 4 dpi (less than or equal to half of baseline values), except for macaque #1 in the R. parkeri-only group, with values returning to baseline in all animals by the date of necropsy (Fig 2B). There were no apparent relevant differences between treatment groups for the rest of the CBC data.


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)

Evidence of an acute phase inflammatory response in response to R. parkeri inoculation.Comparisons of neutrophil (A), lymphocyte (B), and C-reactive protein (C) concentrations in peripheral blood of all animals at the various time points indicated. Neutrophilia, lymphopenia, and elevated C-reactive protein were noted in the acute phase of infection after R. parkeri inoculation with greater neutrophilia noted in the tick + R. parkeri group. 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.g002: Evidence of an acute phase inflammatory response in response to R. parkeri inoculation.Comparisons of neutrophil (A), lymphocyte (B), and C-reactive protein (C) concentrations in peripheral blood of all animals at the various time points indicated. Neutrophilia, lymphopenia, and elevated C-reactive protein were noted in the acute phase of infection after R. parkeri inoculation with greater neutrophilia noted in the tick + R. parkeri group. 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: No differences in weight or temperature were noted between treatment groups during the study. Mild to marked peripheral lymphadenopathy was noted in all animals from 4 dpi to 11 dpi primarily affecting the axillary lymph nodes. At 1 dpi, moderate neutrophilia (greater than 4-fold pre-inoculation values) was noted in both primates in the tick + R. parkeri group as compared to mild neutrophilia (less than 3-fold baseline concentrations) in both R. parkeri-only primates (Fig 2A). All of these animals had mild neutrophilia at 4 dpi that resolved by the time of necropsy in all animals except for macaque #1 in the tick + R. parkeri group. The tick-only macaque developed mild neutrophilia at 4 dpi (less than 3-fold pre-inoculation levels), with values returning to baseline at necropsy. All of the animals inoculated with R. parkeri were lymphopenic at 1 and 4 dpi (less than or equal to half of baseline values), except for macaque #1 in the R. parkeri-only group, with values returning to baseline in all animals by the date of necropsy (Fig 2B). There were no apparent relevant differences between treatment groups for the rest of the CBC data.

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