Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis
- Molecular and Cell Biology, University of California, Berkeley, United States
- Division of Infectious Disease and Vaccinology, School of Public Health, University of California, Berkeley, United States
- Department of Pathobiological Sciences, Louisiana State University, United States
Figures
Figure 1 with 1 supplement
I.d. infection of Ifnar1-/-;Ifngr1-/- mice with R. parkeri elicits skin lesions that are grossly similar to human eschars.
(a) Representative images of WT, Ifnar1-/-, Ifngr1-/-, and Tlr4-/- single mutant mice, infected intradermally with 107 WT R. parkeri PFU, at 8 d.p.i. WT mice were injected with PBS. White arrows …
Figure 1—figure supplement 1
Ifnar1-/-;Ifngr1-/- mice develop disseminated disease upon intradermal R. parkeri infection.
(a) Representative image of the right flank of CD-1 mice intradermally infected with 107 PFU of R. parkeri. Scale bar, 1 cm. Data are representative from two independent experiments. (b) …
Figure 2 with 1 supplement
I.d. infection of Ifnar1-/-;Ifngr1-/- mice by R. parkeri elicits disseminated, lethal disease.
(a) Weight changes over time in mice infected i.d. with R. parkeri. Data are shown as a percentage change to initial weight. In the left panel, all mice were infected with 107 PFU of R. parkeri: n = …
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Figure 2—source data 1
I.d. infection of Ifnar1-/-;Ifngr1-/- mice by R. parkeri elicits disseminated, lethal disease.
- https://cdn.elifesciences.org/articles/67029/elife-67029-fig2-data1-v2.xlsx
Figure 2—figure supplement 1
Ifnar1-/- or Ifngr1-/- mice develop limited disease upon intradermal infection, and Ifnar1-/-;Ifngr1-/- develop lesions of dose-dependent severity.
(a) Weight changes over time in mice intradermally infected with 107 PFU of WT R. parkeri. Data are the combination of two independent experiments for WT and three for Ifnar1-/-;Ifngr1-/-; n = 7 …
Figure 3
Pathology of infected Ifnar1-/-;Ifngr1-/- mice reveals necrosis, inflammation, and rickettsial staining of macrophage and neutrophils.
(a–d) Representative images of the skin from WT and Ifnar1-/-;Ifngr1-/- mice, infected i.d. with 103 R. parkeri. Top row panels are skin stained with hematoxylin and eosin. Bottom row panels are a …
Figure 4 with 3 supplements
R. parkeri Sca2 contributes to dissemination from skin to spleens and livers.
(a) Survival of Ifnar1-/-;Ifngr1-/- mice upon i.v. infection with 5 × 106 PFU of R. parkeri. n = 7 (WT), 10 (sca2::Tn), and 7 (MC1_RS08740::Tn R. parkeri) individual mice. Data are the combination …
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Figure 4—source data 1
R. parkeri Sca2 contributes to dissemination from skin to spleens and livers.
- https://cdn.elifesciences.org/articles/67029/elife-67029-fig4-data1-v2.xlsx
Figure 4—figure supplement 1
Intradermal infection of Ifnar1-/-;Ifngr1-/- mice with sca2::Tn R. parkeri causes less severe temperature loss as compared to WT bacteria.
Temperature changes over time in mice infected i.d. with 107 R. parkeri. Data are the combination of two independent experiments; n = 5 (WT), n = 8 (sca2::Tn) individual mice. Each line represents …
Figure 4—figure supplement 2
WT and sca2::Tn R. parkeri elicit similar amounts of vascular damage in skin upon i.d. infection of Ifnar1-/-;Ifngr1-/- mice.
(a) Quantification of fluorescence in mouse skin after i.d. infection. Mice were infected i.d. with 107 R. parkeri and fluorescent dextran was intravenously delivered at 5 d.p.i. Skin was harvested …
Figure 4—figure supplement 3
Sca2 does not significantly enhance R. parkeri avoidance of antibacterial innate immune responses in vitro.
(a) R. parkeri abundance in HMEC-1s, multiplicity of infection (MOI) of 0.2. Data are the combination of three independent experiments, each with two biological replicates. For statistics, a …
Figure 5
ompB mutant R. parkeri elicit no lethality and reduced skin lesion formation in Ifnar1-/-;Ifngr1-/-mice.
(a) Survival of Ifnar1-/-;Ifngr1-/- mice upon i.d. infection with 107 PFU of R. parkeri. n = 6 (WT) and 8 (ompB::TnSTOP) individual mice. Data are the combination of two independent experiments. …
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Figure 5—source data 1
ompB mutant R. parkeri elicit no lethality and reduced skin lesion formation in Ifnar1-/-;Ifngr1-/-mice.
- https://cdn.elifesciences.org/articles/67029/elife-67029-fig5-data1-v2.xlsx
Figure 6
ompB and sca2 mutant R. parkeri elicit immunity in Ifnar1-/-Ifngr1-/- mice.
(a) Survival of immunized and naïve Ifnar1-/-;Ifngr1-/- mice upon i.v. R. parkeri infection. Immunized mice were first infected with 5 × 106 PFU of sca2::Tn or 107 PFU of ompB:TnSTOP R. parkeri and …
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Figure 6—source data 1
ompB and sca2 mutant R. parkeri elicit immunity in Ifnar1-/-Ifngr1-/- mice.
- https://cdn.elifesciences.org/articles/67029/elife-67029-fig6-data1-v2.xlsx
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Biological sample (Mus musculus) | WT C57Bl/6J | Jackson labs | Stock #: 000664 | |
| Biological sample (Mus musculus) | DKO Ifnar1-/-;Ifngr1-/- | Jackson labs | Stock #: 029098 | |
| Biological sample (Mus musculus) | B6.129S2-Ifnar1tm1Agt/Mmjax; aka Ifnar1-/- | Jackson labs | Stock #: 32045-JAX | RRID:MMRRC_032045-JAX |
| Biological sample (Mus musculus) | B6.129S7-Ifngr1tm1Agt/J; akaIfngr1-/- | Jackson labs | Stock #: 003288 | |
| Antibody | I7205 anti-Rickettsia (Rabbit polyclonal) | Dr. Ted Hackstadt | IHC (1:1000);IF (1:1000) | |
| Biological sample (Rickettsia parkeri) | WT R. parkeri strain Portsmouth | Originally from Dr. Chris Paddock (CDC) | ||
| Biological sample (Rickettsia parkeri) | Sca2::Tn R. parkeri | Welch lab (UC Berkeley)PMID:24361066 | ||
| Biological sample (Rickettsia parkeri) | OmpB::TnSTOPR. parkeri | Welch lab (UC Berkeley)PMID:31611642 |
