Inhaled particulate accumulation with age impairs immune function and architecture in human lung lymph nodes.

Older people are particularly susceptible to infectious and neoplastic diseases of the lung and it is unclear how lifelong exposure to environmental pollutants affects respiratory immune function. In an analysis of human lymph nodes (LNs) from 84 organ donors aged 11-93 years, we found a specific age-related decline in lung-associated, but not gut-associated, LN immune function linked to the accumulation of inhaled atmospheric particulate matter. Increasing densities of particulates were found in lung-associated LNs with age, but not in the corresponding gut-associated LNs. Particulates were specifically contained within CD68+CD169- macrophages, which exhibited decreased activation, phagocytic capacity, and altered cytokine production compared with non-particulate-containing macrophages. The structures of B cell follicles and lymphatic drainage were also disrupted in lung-associated LNs with particulates. Our results reveal that the cumulative effects of environmental exposure and age may compromise immune surveillance of the lung via direct effects on immune cell function and lymphoid architecture.

Proleg retractor muscles in Manduca sexta larvae are segmentally different, suggesting anteroposterior specialization.

Manduca sexta larvae are an important model system for studying the neuromechanics of soft body locomotion. They climb on plants using the abdominal prolegs to grip and maneuver in any orientation and on different surfaces. The prolegs grip passively with an array of cuticular hooks, and grip release is actively controlled by retractor muscles inserted into the soft planta membrane at the proleg tip. Until now, the principal planta retractor muscles (PPRMs) in each body segment were thought to be a single fiber bundle originating on the lateral body wall. Here, using high resolution X-ray microtomography of intact animals, we show that the PPRM is a more complex muscle consisting of multiple contractile fibers originating at several distinct sites on the proleg. Furthermore, we show that there are segmental differences in the number and size of some of these fiber groups which suggests that the prolegs may operate differently along the anterior-posterior axis.

The control of nocifensive movements in the caterpillar Manduca sexta.

In response to a noxious stimulus on the abdomen, caterpillars lunge their head towards the site of stimulation. This nocifensive 'strike' behavior is fast (∼0.5 s duration), targeted and usually unilateral. It is not clear how the fast strike movement is generated and controlled, because caterpillar muscle develops peak force relatively slowly (∼1 s) and the baseline hemolymph pressure is low (<2 kPa). Here, we show that strike movements are largely driven by ipsilateral muscle activation that propagates from anterior to posterior segments. There is no sustained pre-strike muscle activation that would be expected for movements powered by the rapid release of stored elastic energy. Although muscle activation on the ipsilateral side is correlated with segment shortening, activity on the contralateral side consists of two phases of muscle stimulation and a marked decline between them. This decrease in motor activity precedes rapid expansion of the segment on the contralateral side, presumably allowing the body wall to stretch more easily. The subsequent increase in contralateral motor activation may slow or stabilize movements as the head reaches its target. Strike behavior is therefore a controlled fast movement involving the coordination of muscle activity on each side and along the length of the body.

Nociceptive neurons respond to multimodal stimuli in Manduca sexta.

The caterpillar Manduca sexta produces a highly stereotyped strike behavior in response to noxious thermal or mechanical stimuli to the abdomen. This rapid movement is targeted to the site of the stimulus, but the identity of the nociceptive sensory neurons are currently unknown. It is also not known whether both mechanical and thermal stimuli are detected by the same neurons. Here, we show that the likelihood of a strike increases with the strength of the stimulus and that activity in nerves innervating the body wall increases rapidly in response to noxious stimuli. Mechanical and thermal stimuli to the dorsal body wall activate the same sensory unit, suggesting it represents a multimodal neuron. This is further supported by the effects of rapidly repeated thermal or mechanical stimuli, which cause a depression of neuronal responsiveness that is generalized across modalities. Mapping the receptive fields of neurons responding to strong thermal stimuli indicates that these multimodal, nociceptive units are produced by class γ multidendritic neurons in the body wall.