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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

Eschars form after intradermal R. parkeri inoculation and are exacerbated by tick feeding during inoculation.Photographs of tick feeding/inoculation lesions of each group at 4 dpi (A-C), the same locations as pictured in B and C at 31–35 dpi (D and E), and another tick feeding/inoculation site at 0 dpi for comparison (F). (A) Tick feeding alone results in cutaneous erythema at 4 dpi. (B) Intradermal inoculation of R. parkeri results in eschar formation (well circumscribed ulcer surrounded by an erythematous halo) at 4 dpi. (C) Intradermal inoculation of R. parkeri during tick feeding results in a large area of necrosis surrounded by erythema at the inoculation site at 4 dpi. (D) R. parkeri inoculation alone results in the formation of a small scar at 35 dpi. (E) A large healing ulcer has replaced the eschar from the tick feeding + R. parkeri animal at 32 dpi. (F) No gross alterations are noted at the time of R. parkeri inoculation (3 days post female tick infestation) for comparison. Black marks were made adjacent to inoculation sites.
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pone.0135175.g004: Eschars form after intradermal R. parkeri inoculation and are exacerbated by tick feeding during inoculation.Photographs of tick feeding/inoculation lesions of each group at 4 dpi (A-C), the same locations as pictured in B and C at 31–35 dpi (D and E), and another tick feeding/inoculation site at 0 dpi for comparison (F). (A) Tick feeding alone results in cutaneous erythema at 4 dpi. (B) Intradermal inoculation of R. parkeri results in eschar formation (well circumscribed ulcer surrounded by an erythematous halo) at 4 dpi. (C) Intradermal inoculation of R. parkeri during tick feeding results in a large area of necrosis surrounded by erythema at the inoculation site at 4 dpi. (D) R. parkeri inoculation alone results in the formation of a small scar at 35 dpi. (E) A large healing ulcer has replaced the eschar from the tick feeding + R. parkeri animal at 32 dpi. (F) No gross alterations are noted at the time of R. parkeri inoculation (3 days post female tick infestation) for comparison. Black marks were made adjacent to inoculation sites.

Mentions: At 4 dpi, the skin at the site of tick infestation in the tick-only animal was diffusely erythematous, raised and thickened, encompassing the majority of the 5-cm tick containment area (Fig 4A). In the R. parkeri-inoculated animals, at 4 dpi, eschars formed at all inoculation sites (Fig 4B). In the R. parkeri-only group, these eschars were characterized by crusted ulcers that measured approximately 0.5–1 cm in diameter and were surrounded by 0.5–1.5 cm erythematous halos. The eschars were larger in both tick + R. parkeri primates, with areas of ulceration measuring up to 1.5 × 3 cm surrounded by diffusely erythematous, raised, and thickened skin of up to 5 cm in diameter (Fig 4C). At 9 dpi, the R. parkeri-only eschars began to heal with scar formation as opposed to increased erythema and ulceration that developed in all tick infestation groups. At necropsy, eschars in the R. parkeri-only primates had been replaced by scars measuring up to 0.1 × 0.3 cm (Fig 4D); whereas, healing ulcers with scar tissue were noted in all tick infestation groups that measured up to approximately 1 × 2 cm in the tick + R. parkeri macaques (Fig 4E). These healing ulcers were surrounded by maculopapular rashes measuring approximately 3–6 by 4.5–6 cm in both of the tick + R. parkeri macaques.


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)

Eschars form after intradermal R. parkeri inoculation and are exacerbated by tick feeding during inoculation.Photographs of tick feeding/inoculation lesions of each group at 4 dpi (A-C), the same locations as pictured in B and C at 31–35 dpi (D and E), and another tick feeding/inoculation site at 0 dpi for comparison (F). (A) Tick feeding alone results in cutaneous erythema at 4 dpi. (B) Intradermal inoculation of R. parkeri results in eschar formation (well circumscribed ulcer surrounded by an erythematous halo) at 4 dpi. (C) Intradermal inoculation of R. parkeri during tick feeding results in a large area of necrosis surrounded by erythema at the inoculation site at 4 dpi. (D) R. parkeri inoculation alone results in the formation of a small scar at 35 dpi. (E) A large healing ulcer has replaced the eschar from the tick feeding + R. parkeri animal at 32 dpi. (F) No gross alterations are noted at the time of R. parkeri inoculation (3 days post female tick infestation) for comparison. Black marks were made adjacent to inoculation sites.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0135175.g004: Eschars form after intradermal R. parkeri inoculation and are exacerbated by tick feeding during inoculation.Photographs of tick feeding/inoculation lesions of each group at 4 dpi (A-C), the same locations as pictured in B and C at 31–35 dpi (D and E), and another tick feeding/inoculation site at 0 dpi for comparison (F). (A) Tick feeding alone results in cutaneous erythema at 4 dpi. (B) Intradermal inoculation of R. parkeri results in eschar formation (well circumscribed ulcer surrounded by an erythematous halo) at 4 dpi. (C) Intradermal inoculation of R. parkeri during tick feeding results in a large area of necrosis surrounded by erythema at the inoculation site at 4 dpi. (D) R. parkeri inoculation alone results in the formation of a small scar at 35 dpi. (E) A large healing ulcer has replaced the eschar from the tick feeding + R. parkeri animal at 32 dpi. (F) No gross alterations are noted at the time of R. parkeri inoculation (3 days post female tick infestation) for comparison. Black marks were made adjacent to inoculation sites.
Mentions: At 4 dpi, the skin at the site of tick infestation in the tick-only animal was diffusely erythematous, raised and thickened, encompassing the majority of the 5-cm tick containment area (Fig 4A). In the R. parkeri-inoculated animals, at 4 dpi, eschars formed at all inoculation sites (Fig 4B). In the R. parkeri-only group, these eschars were characterized by crusted ulcers that measured approximately 0.5–1 cm in diameter and were surrounded by 0.5–1.5 cm erythematous halos. The eschars were larger in both tick + R. parkeri primates, with areas of ulceration measuring up to 1.5 × 3 cm surrounded by diffusely erythematous, raised, and thickened skin of up to 5 cm in diameter (Fig 4C). At 9 dpi, the R. parkeri-only eschars began to heal with scar formation as opposed to increased erythema and ulceration that developed in all tick infestation groups. At necropsy, eschars in the R. parkeri-only primates had been replaced by scars measuring up to 0.1 × 0.3 cm (Fig 4D); whereas, healing ulcers with scar tissue were noted in all tick infestation groups that measured up to approximately 1 × 2 cm in the tick + R. parkeri macaques (Fig 4E). These healing ulcers were surrounded by maculopapular rashes measuring approximately 3–6 by 4.5–6 cm in both of the tick + R. parkeri macaques.

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