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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

Rickettsial DNA was detected in the skin of R. parkeri-inoculated animals at 4 and 9 dpi.Rickettsial load as detected by qPCR in skin samples from 4 and 9 dpi expressed as R. parkeri ompB copies per 10,000 M. mulatta OSM copies. No rickettsial DNA was isolated from the tick-only macaque at any time point.
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pone.0135175.g007: Rickettsial DNA was detected in the skin of R. parkeri-inoculated animals at 4 and 9 dpi.Rickettsial load as detected by qPCR in skin samples from 4 and 9 dpi expressed as R. parkeri ompB copies per 10,000 M. mulatta OSM copies. No rickettsial DNA was isolated from the tick-only macaque at any time point.

Mentions: R. parkeri DNA was detected in the skin at the inoculation site in all of the R. parkeri-inoculated animals via qPCR at 4 and 9 dpi, with lower copy numbers detected in both tick + R. parkeri animals at 9 dpi (Fig 7). Furthermore, R. parkeri DNA was detected at the cutaneous inoculation site at necropsy and in a lymph node at 4 dpi from the tick + R. parkeri monkey #2. No rickettsial DNA was detected in the other tissue or blood samples from any animal via qPCR, including all tissues from the tick-only group at all time points, the extraction and negative control samples. qPCR positive tissue samples were then subjected to traditional PCR for sequencing of a segment of rickettsial ompA. Sequence analysis of amplicons from all of the qPCR positive tissue samples revealed a sequence identity of ≥ 99% with several different strains of R. parkeri (GenBank accession numbers CP00341.1, KF782320.1, U43802.1, FJ986616.1, JX134641.1, KC003476.1, EU715288.1, and FJ172358.1). No amplicons were observed after traditional PCR using skin DNA extracts at the site of tick infestation from the tick-only animals at 4 and 9 dpi as template. Ten of 26 (38%) engorged female ticks collected in this experiment laid eggs that produced viable larvae. Rickettsial DNA was detected in one of the 10 larval pools (10% positive). This larval pool came from a female tick from the R. parkeri + tick macaque #2. Sequence analysis of this amplicon revealed a sequence identity of 100% to two strains of Candidatus “Rickettsia andeanae” (GenBank accession numbers KF179352.1 and KF030932.1).


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)

Rickettsial DNA was detected in the skin of R. parkeri-inoculated animals at 4 and 9 dpi.Rickettsial load as detected by qPCR in skin samples from 4 and 9 dpi expressed as R. parkeri ompB copies per 10,000 M. mulatta OSM copies. No rickettsial DNA was isolated from the tick-only macaque at any time point.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0135175.g007: Rickettsial DNA was detected in the skin of R. parkeri-inoculated animals at 4 and 9 dpi.Rickettsial load as detected by qPCR in skin samples from 4 and 9 dpi expressed as R. parkeri ompB copies per 10,000 M. mulatta OSM copies. No rickettsial DNA was isolated from the tick-only macaque at any time point.
Mentions: R. parkeri DNA was detected in the skin at the inoculation site in all of the R. parkeri-inoculated animals via qPCR at 4 and 9 dpi, with lower copy numbers detected in both tick + R. parkeri animals at 9 dpi (Fig 7). Furthermore, R. parkeri DNA was detected at the cutaneous inoculation site at necropsy and in a lymph node at 4 dpi from the tick + R. parkeri monkey #2. No rickettsial DNA was detected in the other tissue or blood samples from any animal via qPCR, including all tissues from the tick-only group at all time points, the extraction and negative control samples. qPCR positive tissue samples were then subjected to traditional PCR for sequencing of a segment of rickettsial ompA. Sequence analysis of amplicons from all of the qPCR positive tissue samples revealed a sequence identity of ≥ 99% with several different strains of R. parkeri (GenBank accession numbers CP00341.1, KF782320.1, U43802.1, FJ986616.1, JX134641.1, KC003476.1, EU715288.1, and FJ172358.1). No amplicons were observed after traditional PCR using skin DNA extracts at the site of tick infestation from the tick-only animals at 4 and 9 dpi as template. Ten of 26 (38%) engorged female ticks collected in this experiment laid eggs that produced viable larvae. Rickettsial DNA was detected in one of the 10 larval pools (10% positive). This larval pool came from a female tick from the R. parkeri + tick macaque #2. Sequence analysis of this amplicon revealed a sequence identity of 100% to two strains of Candidatus “Rickettsia andeanae” (GenBank accession numbers KF179352.1 and KF030932.1).

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