Colonization of dermal arterioles by Neisseria meningitidis provides a safe haven from neutrophils.

The human pathogen Neisseria meningitidis can cause meningitis and fatal systemic disease. The bacteria colonize blood vessels and rapidly cause vascular damage, despite a neutrophil-rich inflammatory infiltrate. Here, we use a humanized mouse model to show that vascular colonization leads to the recruitment of neutrophils, which partially reduce bacterial burden and vascular damage. This partial effect is due to the ability of bacteria to colonize capillaries, venules and arterioles, as observed in human samples. In venules, potent neutrophil recruitment allows efficient bacterial phagocytosis. In contrast, in infected capillaries and arterioles, adhesion molecules such as E-Selectin are not expressed on the endothelium, and intravascular neutrophil recruitment is minimal. Our results indicate that the colonization of capillaries and arterioles by N. meningitidis creates an intravascular niche that precludes the action of neutrophils, resulting in immune escape and progression of the infection.

Small vessel vasculitis in a patient with botryomycosis.

We describe a 53 year-old woman with primary biliary cirrhosis presenting with left ankle swelling and a purpuric rash. The skin biopsy of the rash revealed a small vessel vasculitis and a botryomycosis with Splendore-Hoeppli phenomenon. Botryomycosis is an uncommon histologic finding of a chronic suppurative bacterial infection whereby bacteria form aggregates, which are surrounded by an eosinophilic matrix. With guidance from the skin biopsy findings, the patient was appropriately treated with antibiotics, resulting in complete resolution of symptoms.

Intravital fluorescence microscopy: a novel tool for the study of the interaction of Staphylococcus aureus with the microvascular endothelium in vivo.

BACKGROUND: The ability of Staphylococcus aureus to adhere to endothelial cells is a major prerequisite for the tissue-invasive stage of bacterial infection. METHODS: To develop a model for the study of endothelial attachment and detachment kinetics of S. aureus within the host's microvasculature in vivo, we labeled inactivated staphylococci with fluorescein isothiocyanate and investigated their interaction with the vascular endothelium of arterioles, capillaries, and venules in the dorsal skin-fold chamber of untreated and tumor necrosis factor (TNF)-alpha-treated hamsters by use of intravital fluorescence microscopy. RESULTS: During the first 20 min after injection, >99% of the bacteria were removed from the microvascular bloodstream. In parallel, single bacteria and bacterial clusters adhered to the endothelial lining of postcapillary venules and to nutritive capillaries. Bacterial adherence to the endothelium of arterioles was only rarely observed. TNF-alpha treatment significantly accelerated bacterial clearance and resulted in a significant increase of venular, but not arteriolar and capillary, bacterial adherence, indicating the venular endothelium to be the target structure for bacterial recruitment. CONCLUSION: The insights into host-pathogen interaction gained with this new in vivo model offer highly promising novel aspects of the understanding of infections caused by S. aureus.

The effects of Escherichia coli S-fimbriae and outer membrane protein A on rat pial arterioles.

Cerebral vascular injury is common in bacterial meningitis, but the role of microbial factors associated with this phenomenon is unclear. Escherichia coli S-fimbriae and outer membrane protein A (OmpA) have been shown to promote binding and invasion of E. coli to brain microvascular endothelial cells, respectively. Using the cranial window model, we compared the response of pial arterioles in experimental animals exposed to E. coli with and without S-fimbriae or OmpA after intracarotid injection to animals receiving saline (control). After 3 h, pial arteriolar diameter had progressively increased to 144 +/- 23 (SD)% of the baseline value in animals exposed to S-fimbriated E. coli and to 131 +/- 12% of the baseline value in animals exposed to nonfimbriated E. coli. Analysis of variance with Bonferroni post hoc comparisons revealed that at 2 h the pial arteriolar response to S-fimbriated E. coli was significantly different from control (p = 0.0142). After 3 h, the S-fimbriated E. coli group was significantly different from both the control and the nonfimbriated group (p = 0.0024 and 0.0163, respectively). The nonfimbriated group showed a trend of progressive vasodilation, which was not significantly different from the control. After 3 h, pial arteriolar diameter progressively increased to 156 +/- 14% of baseline in animals exposed to OmpA+ E. coli and 151 +/- 24% of baseline to OmpA- E. coli. The vasodilatory response to OmpA+ and OmpA- E. coli was statistically different from control (p = 0.0004 and 0.0010, respectively) but not different from each other. These data suggest that, although cerebral vasodilatory response to E. coli is multifactorial, binding plays an important role in initiating the vasodilation and bacterial invasion does not enhance the vasodilatory response in the cerebral microvasculature.

Lack of direct endotoxin-induced vasoactive effects on isolated skeletal muscle arterioles.

Septic shock continues to be a major cause of mortality in the intensive care unit. This study was conducted to determine if endotoxin exerts a direct effect on the major determinant of peripheral vascular resistance, skeletal muscle arterioles. First order cremasteric arterioles were isolated from male Sprague-Dawley rats, cannulated with glass micropipettes, superfused in physiologic saline solution, and allowed to achieve spontaneous basal tone in the absence of intraluminal flow. Phenylephrine responsiveness was assessed before and after exposure to 2.5 micrograms/mL Salmonella enteritidis endotoxin (ET) for 1-2 h. There was no change in either basal diameter (91 +/- 5 microns before ET and 98 +/- 5 microns after ET) or phenylephrine responsiveness. In vivo exposure to ET (15 mg/kg) resulted in no change in basal tone at 1 h, however increased tone was observed in arterioles harvested after 4 h of systemic ET (43 +/- 4% without ET and 57 +/- 3% with, p < .05). To determine if upstream conduit vessels released factors responsible for the vasodilation of skeletal muscle arterioles, isolated cannulated cremasteric arterioles were connected in series to a 1 cm segment of aorta and superfused without and with 2.5 micrograms/mL ET. An increase in basal diameter was observed in arterioles from 94 +/- 14 microns before ET to 120 +/- 17 microns after ET (p < .05). These studies demonstrate that ET has no direct effect on isolated cannulated skeletal muscle arterioles, and that a vasodilating substance not consistent with nitric oxide is released from the upstream arterial bed.

An electron microscopic study of the small cutaneous vessels in lepromatous leprosy.

The small dermal vessels play an important role for the propagation of Mycobacterium leprae. Bacteria can multiply in the endothelial cells as well as in the pericytes and can enter the blood stream from the endothelial cells and the interstitial space from the pericytes. M. leprae can be phagocytosed by blood monocytes.

Lyme arthritis. Spirochetes found in synovial microangiopathic lesions.

In 17 patients with Lyme disease, synovial specimens, obtained by synovectomy or needle biopsy, showed nonspecific villous hypertrophy, synovial cell hyperplasia, prominent microvasculature, lymphoplasmacellular infiltration, and sometimes lymphoid follicles. The larger surgically obtained specimens also showed striking deposition of fibrin in synovial stroma and a form of endarteritis obliterans. In 2 patients, spirochetes were seen in and around blood vessels by the Dieterle silver stain. Compared with 55 cases of other synovial disease, obliterative microvascular lesions were seen only in Lyme synovia, but marked stromal deposition of fibrin seemed nonspecific. These findings imply that the Lyme spirochete may survive for years in affected synovium and may be directly responsible for the microvascular injury.