Experimental cutaneous Bacillus anthracis infections in hairless HRS/J mice.

Division of Infectious Diseases, Department of Medicine, Medical College of Wisconsin, and Consultant Care Division and Research Service, VA Medical Center, Milwaukee, WI 53295, USA.
International Journal of Experimental Pathology (Impact Factor: 2.05). 03/2007; 88(1):75-84. DOI: 10.1111/j.1365-2613.2006.00519.x
Source: PubMed

ABSTRACT Previous studies of experimental Bacillus anthracis cutaneous infections in mice have implicated hair follicles as a likely entry site. Hairless HRS/J mice were used to investigate this possibility because of their non-functional hair follicles that lack penetrating hair shafts. These mice also have diminished macrophage function, increased susceptibility to Listeria, and enhanced neutrophil responses. HRS/J and Balb/c mice were found to be resistant to epicutaneous inoculation with Bacillus anthracis (Sterne) spores onto abraded skin when compared with DBA/2 mice or leucopenic C57BL/6 mice. The HRS/J mice also resisted spore injections that bypassed hair follicles. Haired HRS/J heterozygote mice demonstrated similar reduced susceptibility to B. anthracis spores. Hairless HRS/J mice that were made leucopenic did become susceptible to the epicutaneous spore inoculations. Histologically, the hairless and haired HRS/J mice showed markedly reduced numbers of organisms in hair follicles and the interfollicular dermis when compared even with the resistant Balb/c mice; inflammatory cell infiltrates in the superficial dermis were increased in the HRS/J mice compared with more sensitive strains. Therefore, resistance in the HRS/J mice was apparent at the initial site of epicutaneous inoculation and seemed related to an accumulation of dermal neutrophils rather than to a lack of functional hair follicles.

Download full-text


Available from: Beth L Hahn, Jul 29, 2015
  • Source
    • "When skin is abraded, as is readily evident from skin window studies in humans, there is a brisk exudation of host inflammatory cells that are primarily neutrophils (Wandall 1980; Yee et al. 1994; Koivuranta-Vaara 1985). We have previously found a similar exudation of inflammatory cells, predominantly neutrophils, in the abraded skin of mouse strains such as C57BL ⁄ 6, DBA ⁄ 2, and HRS ⁄ J hr ⁄ hr (Bischof et al. 2007a). Also, neutrophils from humans and mice have been found to be capable of killing B. anthracis spores and ⁄ or bacilli in vitro (Welkos et al. 1989; Mayer-Scholl et al. 2005); in fact, in one study encapsulated bacilli of the B. anthracis Vollum strain were phagocytosed and killed efficiently by human neutrophils through a mechanism dependent upon a-defensins (Mayer- Scholl et al. 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Skin window procedures in humans have shown rapid accumulation of neutrophils into the exuded fluids above abraded skin. The present study was undertaken to determine if similar epicutaneous neutrophil accumulation might explain the extreme resistance of HRS/J mice, both hairless (hr/hr) and haired (hr/+), to experimental cutaneous Bacillus anthracis Sterne infections on abraded skin. In this study, very early (6 h) biopsies demonstrated a lack of bacilli in skin from the HRS/J hr/hr mice, indicating that the organisms never did invade in these animals as opposed to early skin entry and then efficient clearance by host responses in the tissues. Touch preparations of either the inoculation filter or the skin surface revealed more inflammatory cells, fewer bacilli, and a higher percentage of cell-associated bacilli in the HRS/J hr/hr mice than in comparator strains. In the HRS/J mice, cyclophosphamide treatment or separation of inoculated spores from the inflammatory infiltrates by a second filter below both produced marked increases in the number of bacilli observed. Examination of inoculation filter specimens demonstrated ingestion of spores and bacilli by neutrophils inside the filter at 6 h after inoculation. These findings suggest that an early and vigorous inflammatory cell infiltrate in HRS/J mice attacks the inoculated organisms above the skin surface and does not allow them to invade the tissues below.
    International Journal of Experimental Pathology 07/2008; 89(3):180-7. DOI:10.1111/j.1365-2613.2008.00584.x · 2.05 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hair follicles may allow pathogen entry because they represent potential barrier defects and because there is immunological privilege within actively growing follicles. Experimental cutaneous Bacillus anthracis infections in mice have previously shown prominent organism invasion and proliferation within hair follicles. For the present study, C57BL/6 mice were inoculated with B. anthracis (Sterne) spores onto abraded skin with either anagen (actively growing) or telogen (inactive) hair follicles; skin samples were evaluated by histologic methods and electron microscopy. The infections were found to progress similarly in either anagen or telogen hair follicles, with bacilli occasionally invading deeper sites in anagen hair follicles. The infections progressed from the surface inward, rather than growing outward from within the follicles. Infecting bacilli destroyed the hair follicle keratinocytes and were initially not contacted by inflammatory cells within the follicles. However, at 3-4 days after inoculation, inflammatory cells did contact and disperse the massed follicle bacilli and led to apparent resolution of the follicle infections. Therefore, in this model system B. anthracis initially attacks superficial sites in active or inactive hair follicles and then progresses inward, producing destructive infections of the hair follicles; these infections clear when the massed bacilli are eventually contacted and dispersed by inflammatory cells.
    Microbial Pathogenesis 06/2008; 44(5):363-9. DOI:10.1016/j.micpath.2007.10.011 · 2.00 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies in a murine cutaneous anthrax model have demonstrated that hairless and haired HRS/J mice are extremely resistant to Bacillus anthracis. Because these mice are relatively thymus deficient, we used C57BL/6 athymic nude and euthymic mice to evaluate the relationship between T cell deficiency and this heightened resistance. Animals were epicutaneously inoculated with 1 X 10(7) B. anthracis (Sterne) spores onto abraded skin or injected with the spores intradermally or subcutaneously. The mice were then either monitored for survival or killed for quantitative histological experiments. Athymic mice were found to be markedly resistant to all 3 inoculation routes, compared with euthymic C57BL/6 mice. Athymic mice rendered leukopenic with cyclophosphamide became susceptible. Histological examination demonstrated increased inflammation and absence of organisms in the skin of athymic mice, compared with euthymic ones. The numbers of organisms in the athymic animals increased markedly after cyclophosphamide treatment. Superficial exudate fluids of inoculated skin showed many more neutrophils and ingested bacilli in the athymic mice. These experiments demonstrate that athymic nude C57BL/6 mice are markedly resistant to experimental cutaneous anthrax, apparently because of a superficial neutrophilic response that clears the inoculated organisms before they can invade the underlying skin.
    The Journal of Infectious Diseases 02/2009; 199(5):673-9. DOI:10.1086/596631 · 5.78 Impact Factor
Show more