Experience-dependent olfactory behaviors of the parasitic nematode Heligmosomoides polygyrus

Abstract

Parasitic nematodes of humans and livestock cause extensive disease and economic loss worldwide. Many parasitic nematodes infect hosts as third-stage larvae, called iL3s. iL3s vary in their infection route: some infect by skin penetration, others by passive ingestion. Skin-penetrating iL3s actively search for hosts using host-emitted olfactory cues, but the extent to which passively ingested iL3s respond to olfactory cues was largely unknown. Here, we examined the olfactory behaviors of the passively ingested murine gastrointestinal parasite Heligmosomoides polygyrus. H. polygyrus iL3s were thought to reside primarily on mouse feces, and infect when mice consume feces containing iL3s. However, iL3s can also adhere to mouse fur and infect orally during grooming. Here, we show that H. polygyrus iL3s are highly active and show robust attraction to host feces. Despite their attraction to feces, many iL3s migrate off feces to engage in environmental navigation. In addition, H. polygyrus iL3s are attracted to mammalian skin odorants, suggesting that they migrate toward hosts. The olfactory preferences of H. polygyrus are flexible: some odorants are repulsive for iL3s maintained on feces but attractive for iL3s maintained off feces. Experience-dependent modulation of olfactory behavior occurs over the course of days and is mediated by environmental carbon dioxide (CO ₂) levels. Similar experience-dependent olfactory plasticity occurs in the passively ingested ruminant-parasitic nematode Haemonchus contortus, a major veterinary parasite. Our results suggest that passively ingested iL3s migrate off their original fecal source and actively navigate toward hosts or new host fecal sources using olfactory cues. Olfactory plasticity may be a mechanism that enables iL3s to switch from dispersal behavior to host-seeking behavior. Together, our results demonstrate that passively ingested nematodes do not remain inactive waiting to be swallowed, but rather display complex sensory-driven behaviors to position themselves for host ingestion. Disrupting these behaviors may be a new avenue for preventing infections.

Author summary

Many parasitic nematodes infect by passive ingestion when the host consumes food, water, or feces containing infective third-stage larvae (iL3s). Passively ingested nematodes that infect humans cause severe gastrointestinal distress and death in endemic regions, and those that infect livestock are a major cause of production loss worldwide. Because these parasites do not actively invade hosts but instead rely on being swallowed by hosts, it has been assumed that they show only limited sensory responses and do not engage in host-seeking behaviors. Here, we investigate the olfactory behaviors of the passively ingested murine parasite Heligmosomoides polygyrus and show that this assumption is incorrect; H. polygyrus iL3s show robust attraction to a diverse array of odorants found in mammalian skin, sweat, and feces. Moreover, the olfactory responses of H. polygyrus iL3s are experience-dependent: some odorants are repulsive to iL3s cultured on feces but attractive to iL3s removed from feces. Olfactory plasticity is also observed in the ruminant parasite Haemonchus contortus, and may enable iL3s to disperse in search of new hosts or host fecal sources. Our results suggest that passively ingested nematodes use olfactory cues to navigate their environments and position themselves where they are likely to be swallowed. By providing new insights into the olfactory behaviors of these parasites, our results may enable the development of new strategies for preventing infections.