These data demonstrate that the presence of commensal bacteria is critical for ensuring normal cellular maturation, recruitment, and control of allergic airway inflammation.
Basophils are powerful mediators of Th2 immunity and are present in increased numbers during allergic inflammation and helminth infection. Despite their ability to potentiate Th2 immunity the mechanisms regulating basophil development remain largely unknown. We have found a unique role for isotype-switched antibodies in promoting helminth-induced basophil production following infection of mice with
Heligmosomoides polygyrus bakeri
or
Nippostrongylus brasiliensis
.
H. polygyrus bakeri
-induced basophil expansion was found to occur within the bone marrow, and to a lesser extent the spleen, and was IL-3 dependent. IL-3 was largely produced by CD4
+
CD49b
+
NK1.1
−
effector T cells at these sites, and required the IL-4Rα chain. However, antibody-deficient mice exhibited defective basophil mobilization despite intact T-cell IL-3 production, and supplementation of mice with immune serum could promote basophilia independently of required IL-4Rα signaling. Helminth-induced eosinophilia was not affected by the deficiency in isotype-switched antibodies, suggesting a direct effect on basophils rather than through priming of Th2 responses. Although normal type 2 immunity occurred in the basopenic mice following primary infection with
H. polygyrus bakeri
, parasite rejection following challenge infection was impaired. These data reveal a role for isotype-switched antibodies in promoting basophil expansion and effector function following helminth infection.
In an attempt to overcome infections associated with central venous catheters, a new antiseptic central venous catheter coated with benzalkonium chloride on the internal and external surfaces has been developed and evaluated in a clinical trial. Patients (235) randomly received either a triple-lumen central venous catheter coated with benzalkonium chloride (117) or a polyurethane non-antiseptic catheter (118). The incidence of microbial colonization of both catheters and retained antiseptic activity of the benzalkonium chloride device following removal were determined. The benzalkonium chloride resulted in a significant reduction of the incidence of microbial colonization on both the internal and external catheter surfaces. The reduction in colonization was detected at both the intradermal (21 benzalkonium chloride catheters vs. 38 controls, P = 0.0016) and distal segments of the antiseptic-coated catheters. Following catheter removal retained activity was demonstrated in benzalkonium chloride catheters which had been in place for up to 12 days. No patients developed adverse reactions to the benzalkonium chloride catheters. The findings demonstrate that the benzalkonium chloride catheter significantly reduced the incidence of catheter-associated colonization.
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