Staphylococcus aureus is the aetiological agent of many hospital-and communityacquired infections. Toll-like receptor 2 (TLR2) has been shown to play a crucial role in the host defence against S. aureus infection. The aim of this study is to investigate the roles of the heterogeneous TLR family proteins TLR2, TLR4 and RP105 during S. aureus infection. Peritoneal macrophages from mice were exposed to S. aureus. Their production of inflammatory cytokines and chemokines, their expression of cell-surface markers and interactions between TLR2, TLR4 and RP105 were assessed in the presence or absence of inhibitory antibodies against TLR2, TLR4/MD-2 and RP105/MD-1 complexes. Our results demonstrate that not only TLR2 but also TLR4 and RP105 are involved in the response of macrophages to S. aureus, that TLR2, TLR4 and RP105 physically interact with each other during S. aureus infection, and that TLR2, TLR4 and RP105 both cooperate and play unique roles in the production of inflammatory cytokines (TNF-a, IL-12p40 and IL-10) and chemokine (RANTES) by macrophages after S. aureus infection. This study characterizes the important roles that TLR2, TLR4 and RP105 play in host resistance against S. aureus infection.
Of 199 patients with baseline lipid assessments, 14.6% (29) and 18.6% (37) had had elevated LDL and total cholesterol respectively by AAP criteria. Craniopharyngioma was the most common diagnosis associated with elevated LDL (31%), total cholesterol (35.1%), and overweight or obese BMI (39%) at diagnosis. Elevated LDL alone or in combination with risk factors including HTN, smoking, or diabetes warranted consideration of pharmacologic intervention in 6.2% of patients at diagnosis. At six and 12 months following radiotherapy, 24.7% and 21% of patients met criteria for either borderline or elevated fasting LDL or total cholesterol suggesting the need for dietary modification or pharmacological intervention. Radiotherapy to the hypothalamus or pituitary did not modify the risk for worsening total or LDL cholesterol relative to baseline at 6 or 12 months at these early time-points, although further follow-up is needed. Conclusion: Pediatric patients had higher than expected rates of borderline or elevated LDL or total cholesterol at baseline and in follow-up relative to the general population despite their cancer diagnosis suggesting the need for nutritional and/or endocrine evaluation at diagnosis and in follow-up. Screening and counseling for modifiable risk factors are warranted given the known association of site specific radiotherapy with increased incidence of CVD and metabolic syndrome.
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