Helminth infections induce Th2-type biased immune responses. Although the mechanisms involved in this phenomenonare not yet clearly defined, antigen-presenting cells (APC) could play an important role in this process. Here, we have used peritoneal macrophages (F4/80؉) recruited at different times after challenge with Taenia crassiceps as APC and tested their ability to regulate Th1/Th2 differentiation. Macrophages from acute infections produced high levels of interleukin-12 (IL-12) and nitric oxide (NO), paralleled with low levels of IL-6 and prostaglandin E 2 (PGE 2 ) and with the ability to induce strong antigen-specific CD4؉ T-cell proliferation in response to nonrelated antigens. In contrast, macrophages from chronic infections produced higher levels of IL-6 and PGE 2 and had suppressed production of IL-12 and NO, associated with a poor ability to induce antigen-specific proliferation in CD4 ؉ T cells. Failure to induce proliferation was not due to a deficient expression of accessory molecules, since major histocompatibility complex class II, CD40, and B7-2 were up-regulated, together with CD23 and CCR5 as infection progressed. These macrophages from chronic infections were able to bias CD4 ؉ T cells to produce IL-4 but not gamma interferon (IFN-␥), contrary to macrophages from acute infections. Blockade of B7-2 and IL-6 and inhibition of PGE 2 failed to restore the proliferative response in CD4 ؉ T cells. Furthermore, studies using STAT6 ؊/؊ mice revealed that STAT6-mediated signaling was essential for the expansion of these alternatively activated macrophages. These data demonstrate that helminth infections can induce different macrophage populations that have Th2-biasing properties.

An increase in hemoglobin concentration during exercise compensates for the decline in arterial oxygen saturation, meanwhile arterial oxygen content remains constant.

Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are essential regulators of synaptic function in the adult CNS. A TrkB-mediated effect at excitatory synapses is enhancement of NMDA receptor (NMDA-R)-mediated currents. Recently, opposing effects of TrkB and the pan-neurotrophin receptor p75 NTR on long-term synaptic depression and long-term potentiation have been reported in the hippocampus. To further study the regulation of NMDA-Rs by neurotrophin receptors in their native protein environment, we micro-transplanted rat forebrain post-synaptic densities (PSDs) into Xenopus oocytes. One-minute incubations of oocytes with BDNF led to dual effects on NMDA-R currents: either TrkB-dependent potentiation or TrkB-independent inhibition were observed. Pro-nerve growth factor, a ligand for p75 NTR but not for TrkB, produced a Neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), bind to two structurally unrelated receptors, Trk receptor tyrosine kinases and the p75 NTR receptor. NGF and BDNF act selectively on TrkA and TrkB, respectively, triggering well characterized intracellular cascades, but also acting directly on ionic channels on a rapid time scale (Huang and Reichardt 2003 These authors contributed equally to this work.Abbreviations used: BDNF, brain-derived neurotrophic factor; LTP, long-term potentiation; NGF, nerve growth factor; PSD, post-synaptic density; MBP, maltose-binding protein.

We previously showed that arterial oxygen content during maximum exercise remains constant at high altitude (HA) in miners exposed to chronic intermittent hypobaric hypoxia (CIHH). Nevertheless, information about VO2, lactate concentration [Lac], and work efficiency are absent in this CIHH miner population. Our aim was to determine aerobic capacity, [Lac], and work efficiency at sea level (SL) and HA during maximum exercise in miners acclimatized to CIHH at 3,800 m. Eight volunteer miners acclimatized to CIHH at HA (> 4 years) performed an exercise test at SL and HA. The test was performed on the 4th day at HA or SL and consisted of three phases: Rest (5 min); Exercise test, where the load was increased by 50 W every 3 min until exhaustion; and a Recovery period of 30 min. During the procedure VO2, transcutaneous arterial saturation (SpO2, %), and HR (bpm) were assessed at each step by a pulse oximeter and venous blood samples were taken to measure [Lac] and hemoglobin concentration. No differences in VO2 and [Lac] in SL vs. HA were observed in this CIHH miner population. By contrast, a higher HR and lower SpO2 were observed at SL compared with HA. During maximum exercise, a reduction in VO2 and [Lac] was observed without differences in intensity (W) and HR. A decrease in [Lac] was observed at maximum effort (250 W) and recovery at HA vs. SL. These findings are related to an increased work efficiency assessment such as gross and net efficiency. This study is the first to show that miners exposed to CIHH maintain their work capacity (intensity) with a fall in oxygen consumption and a decrease in plasmatic lactate concentration at maximal effort at HA. These findings indicate that work efficiency at HA is enhanced.