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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

Intradermal inoculation of R. parkeri results in marked diffuse dermatitis characterized by infiltrates of neutrophils and macrophages, epidermal necrosis, and dermal vasculitis at 4 dpi.Photomicrographs of an H&E-stained skin section from a primate from the R. parkeri-only group at 4 dpi. (A) The epidermis is diffusely necrotic and superficial dermis is effaced by inflammatory cells. (B) Magnified view showing a dermal vessel (arrow) effaced by neutrophils and macrophages (vasculitis) and another dermal vessel with intact endothelium (arrowhead) surrounded by neutrophils and macrophages.
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pone.0135175.g005: Intradermal inoculation of R. parkeri results in marked diffuse dermatitis characterized by infiltrates of neutrophils and macrophages, epidermal necrosis, and dermal vasculitis at 4 dpi.Photomicrographs of an H&E-stained skin section from a primate from the R. parkeri-only group at 4 dpi. (A) The epidermis is diffusely necrotic and superficial dermis is effaced by inflammatory cells. (B) Magnified view showing a dermal vessel (arrow) effaced by neutrophils and macrophages (vasculitis) and another dermal vessel with intact endothelium (arrowhead) surrounded by neutrophils and macrophages.

Mentions: The cutaneous histologic findings are summarized in Table 2. At 4 dpi, marked, diffuse dermatitis extending throughout the superficial and deep dermis and characterized by infiltration of many neutrophils and fewer macrophages was observed in all macaques, except the R. parkeri-only macaque #1, which had a moderate perivascular dermatitis consisting primarily of neutrophils with fewer macrophages. Epidermal necrosis was found only in the R. parkeri-inoculated animals (Fig 5A and 5B, Table 2). At 9 dpi, moderate to marked diffuse infiltration of the superficial and deep dermis by macrophages and neutrophils was noted in the tick + R. parkeri animals with moderate to marked epidermal necrosis, as opposed to mild perivascular dermatitis characterized by aggregates of variable numbers of neutrophils, macrophages, lymphocytes and plasma cells noted in the tick-only and R. parkeri-only macaques with mild epidermal necrosis in the R. parkeri-only animals. At 17 dpi and at necropsy, mild to moderate perivascular lymphocytic to lymphoplasmacytic inflammation was noted in the tick infestation groups with mild to moderate epidermal necrosis noted in the tick + R. parkeri group at 17 dpi and mild epidermal necrosis in the tick-only group at 31 dpi. The R. parkeri-only group had no significant histopathological lesions at these time points except for the R. parkeri-only macaque #1, which had mild perivascular lymphoplasmacytic inflammation at necropsy. Furthermore, marked dermal vasculitis was noted in the R. parkeri-only macaque #2 at 4dpi with mild vasculitis noted in the tick + R. parkeri animal #1 at 4 and 9 dpi. This vasculitis was characterized by intramural fibrin deposition, endothelial cell necrosis/degeneration, and/or inflammatory cells (neutrophils and macrophages) within vessel walls (as depicted in Fig 5B). Mild to moderate lymphadenitis characterized by infiltrates of macrophages and neutrophils with lymphoid hyperplasia was noted in all animals at various time points after inoculation/infestation. No other significant lesions were noted in the other tissues collected. Immunohistochemical staining revealed few to many positively staining coccobacilli primarily within macrophages and fewer within neutrophils in both R. parkeri-inoculated groups at 4 and 9 dpi (Fig 6B and 6C, Table 2). Rare organisms were also noted in macrophages in tick infestation site in the tick-only animal at 4 dpi (Fig 6A, Table 2) and in a lymph node from the tick + R. parkeri macaque #2 at 4 dpi.


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)

Intradermal inoculation of R. parkeri results in marked diffuse dermatitis characterized by infiltrates of neutrophils and macrophages, epidermal necrosis, and dermal vasculitis at 4 dpi.Photomicrographs of an H&E-stained skin section from a primate from the R. parkeri-only group at 4 dpi. (A) The epidermis is diffusely necrotic and superficial dermis is effaced by inflammatory cells. (B) Magnified view showing a dermal vessel (arrow) effaced by neutrophils and macrophages (vasculitis) and another dermal vessel with intact endothelium (arrowhead) surrounded by neutrophils and macrophages.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0135175.g005: Intradermal inoculation of R. parkeri results in marked diffuse dermatitis characterized by infiltrates of neutrophils and macrophages, epidermal necrosis, and dermal vasculitis at 4 dpi.Photomicrographs of an H&E-stained skin section from a primate from the R. parkeri-only group at 4 dpi. (A) The epidermis is diffusely necrotic and superficial dermis is effaced by inflammatory cells. (B) Magnified view showing a dermal vessel (arrow) effaced by neutrophils and macrophages (vasculitis) and another dermal vessel with intact endothelium (arrowhead) surrounded by neutrophils and macrophages.
Mentions: The cutaneous histologic findings are summarized in Table 2. At 4 dpi, marked, diffuse dermatitis extending throughout the superficial and deep dermis and characterized by infiltration of many neutrophils and fewer macrophages was observed in all macaques, except the R. parkeri-only macaque #1, which had a moderate perivascular dermatitis consisting primarily of neutrophils with fewer macrophages. Epidermal necrosis was found only in the R. parkeri-inoculated animals (Fig 5A and 5B, Table 2). At 9 dpi, moderate to marked diffuse infiltration of the superficial and deep dermis by macrophages and neutrophils was noted in the tick + R. parkeri animals with moderate to marked epidermal necrosis, as opposed to mild perivascular dermatitis characterized by aggregates of variable numbers of neutrophils, macrophages, lymphocytes and plasma cells noted in the tick-only and R. parkeri-only macaques with mild epidermal necrosis in the R. parkeri-only animals. At 17 dpi and at necropsy, mild to moderate perivascular lymphocytic to lymphoplasmacytic inflammation was noted in the tick infestation groups with mild to moderate epidermal necrosis noted in the tick + R. parkeri group at 17 dpi and mild epidermal necrosis in the tick-only group at 31 dpi. The R. parkeri-only group had no significant histopathological lesions at these time points except for the R. parkeri-only macaque #1, which had mild perivascular lymphoplasmacytic inflammation at necropsy. Furthermore, marked dermal vasculitis was noted in the R. parkeri-only macaque #2 at 4dpi with mild vasculitis noted in the tick + R. parkeri animal #1 at 4 and 9 dpi. This vasculitis was characterized by intramural fibrin deposition, endothelial cell necrosis/degeneration, and/or inflammatory cells (neutrophils and macrophages) within vessel walls (as depicted in Fig 5B). Mild to moderate lymphadenitis characterized by infiltrates of macrophages and neutrophils with lymphoid hyperplasia was noted in all animals at various time points after inoculation/infestation. No other significant lesions were noted in the other tissues collected. Immunohistochemical staining revealed few to many positively staining coccobacilli primarily within macrophages and fewer within neutrophils in both R. parkeri-inoculated groups at 4 and 9 dpi (Fig 6B and 6C, Table 2). Rare organisms were also noted in macrophages in tick infestation site in the tick-only animal at 4 dpi (Fig 6A, Table 2) and in a lymph node from the tick + R. parkeri macaque #2 at 4 dpi.

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