Peanut butter feeding induces oral tolerance in genetically diverse collaborative cross mice.

Background: Early dietary introduction of peanut has shown efficacy in clinical trials and driven pediatric recommendations for early introduction of peanut to children with heightened allergy risk worldwide. Unfortunately, tolerance is not induced in every case, and a subset of patients are allergic prior to introduction. Here we assess peanut allergic sensitization and oral tolerance in genetically diverse mouse strains. Objective: We aimed to determine whether environmental adjuvant-driven airway sensitization and oral tolerance to peanut could be induced in various genetically diverse mouse strains. Methods: C57BL/6J and 12 Collaborative Cross (CC) mouse strains were fed regular chow or ad libitum peanut butter to induce tolerance. Tolerance was tested by attempting to sensitize mice via intratracheal exposure to peanut and lipopolysaccharide (LPS), followed by intraperitoneal peanut challenge. Peanut-specific immunoglobulins and peanut-induced anaphylaxis were assessed. Results: Without oral peanut feeding, most CC strains (11/12) and C57BL/6J induced peanut-specific IgE and IgG1 following airway exposure to peanut and LPS. With oral peanut feeding none of the CC strains nor C57BL/6J mice became sensitized to peanut or experienced anaphylaxis following peanut challenge. Conclusion: Allergic sensitization and oral tolerance to peanut can be achieved across a range of genetically diverse mice. Notably, the same strains that became allergic via airway sensitization were tolerized by feeding high doses of peanut butter before sensitization, suggesting that the order and route of peanut exposure are critical for determining the allergic fate.

EXPERIMENTAL INFECTIONS WITH EUHAPLORCHIS CALIFORNIENSIS AND A SMALL CYATHOCOTYLID INCREASE CONSPICUOUS BEHAVIORS IN CALIFORNIA KILLIFISH (FUNDULUS PARVIPINNIS).

Some parasites manipulate their host's phenotype to enhance predation rates by the next host in the parasite's life cycle. Our understanding of this parasite-increased trophic transmission is often stymied by study-design challenges. A recurring difficulty has been obtaining uninfected hosts with a coevolutionary history with the parasites, and conducting experimental infections that mimic natural processes. In 1996, Lafferty and Morris provided what has become a classic example of parasite-increased trophic transmission; they reported a positive association between the intensity of a brain-infecting trematode (Euhaplorchis californiensis) in naturally infected California killifish (Fundulus parvipinnis) and the frequency of conspicuous behaviors, which was thought to explain the documented 10-30× increase in predation by the final host birds. Here, we address the primary gap in that study by using experimental infections to assess the causality of E. californiensis infection for increased conspicuous behaviors in F. parvipinnis. We hatched and reared uninfected F. parvipinnis from a population co-occurring with E. californiensis, and infected them 1-2 times/week over half their life span with E. californiensis and a small cyathocotylid trematode (SMCY) that targets the host's muscle tissue. At 3 time points throughout the hosts' lives, we quantified several conspicuous behaviors: contorting, darting, scratching, surfacing, and vertical positioning relative to the water's surface. Euhaplorchis californiensis and SMCY infection caused 1.8- and 2.5-fold overall increases in conspicuous behaviors, respectively. Each parasite was also associated with increases in specific conspicuous behaviors, particularly 1.9- and 1.4-fold more darting. These experimental findings help solidify E. californiensis-F. parvipinnis as a classic example of behavioral manipulation. Yet our findings for E. californiensis infection-induced behavioral change were less consistent and strong than those previously documented. We discuss potential explanations for this discrepancy, particularly the idea that behavioral manipulation may be most apparent when fish are actively attacked by predators. Our findings concerning the other studied trematode species, SMCY, highlight that trophically transmitted parasites infecting various host tissues are known to be associated with conspicuous behaviors, reinforcing calls for research examining how communities of trophically transmitted parasites influence host behavior.

A single priming event prevents oral tolerance to peanut.

BACKGROUND: Indoor dust (ID) is a source of peanut proteins and immunostimulatory adjuvants (e.g. LPS) that can promote airway sensitization to peanut. We aimed to determine whether a single airway exposure to peanut plus adjuvant is sufficient to prevent oral tolerance. METHODS: To determine the effect of a single priming event, C57BL/6J mice were exposed once to peanut plus adjuvant through the airway, followed by either airway or low-dose oral exposure to peanut, and assessed for peanut allergy. Oral tolerance was investigated by feeding high-dose peanut followed by airway sensitization. To determine whether a single priming could prevent oral tolerance, the high-dose peanut regimen was applied after a single airway exposure to peanut plus adjuvant. Peanut-specific IgE and IgG1 were quantified, and mice were challenged to peanut to assess allergy. Peanut-specific CD4+ memory T cells (CD4+ TCRß+ CD44hi CD154+ ) were quantified in mediastinal lymph nodes following airway priming. RESULTS: Mice co-exposed to peanut with LPS or ID through the airway were primed to develop peanut allergy after subsequent low-dose oral or airway exposures to peanut. Oral tolerance was induced in mice fed high-dose peanut prior to airway sensitization. In contrast, mice fed high-dose peanut following a single airway exposure to peanut plus adjuvant led to allergy. Peanut-specific CD4+ memory T cells were detected as early as 7 days after the single airway priming with peanut plus adjuvant, however, delaying peanut feeding even 1 day following priming led to allergy, whereas peanut feeding the same day as priming led to tolerance. CONCLUSIONS: A single airway exposure to peanut plus adjuvant is sufficient to prime the immune system to develop allergy following subsequent high-dose oral exposure. These results highlight the importance of introducing peanut as early as possible to prevent sensitization through a non-oral priming event.

Environmental Exposure to Foods as a Risk Factor for Food Allergy.

PURPOSE OF REVIEW: Many factors have been reported to contribute to the development of food allergy. Here, we summarize the role of environmental exposure to foods as a major risk factor for developing food allergy. RECENT FINDINGS: Peanut proteins are detectable and biologically active in household environments, where infants spend a majority of their time, providing an environmental source of allergen exposure. Recent evidence from clinical studies and mouse models suggests both the airway and skin are routes of exposure that lead to peanut sensitization. Environmental exposure to peanut has been clearly associated with the development of peanut allergy, although other factors such as genetic predisposition, microbial exposures, and timing of oral feeding of allergens also likely contribute. Future studies should more comprehensively assess the contributions of each of these factors for a variety of food allergens to provide more clear targets for prevention of food allergy.

Potential for Emergence of Foodborne Trematodiases Transmitted by an Introduced Snail (Melanoides tuberculata) in California and Elsewhere in the United States.

We document that 3 human-infectious trematodes and their introduced first intermediate host snail (Melanoides tuberculata) are widespread throughout southern California. We surveyed 41 fishing localities, 19 of which harbored snails infected with zoonotic trematodes. Two of the parasites, Haplorchis pumilio and Centrocestus formosanus, are fishborne intestinal trematodes recognized as being important human pathogens in other areas of the world; the third, Philophthalmus gralli, can infect the human eye. An additional 5 species detected infecting M. tuberculata are likely of little direct threat to people; however, they may be recently introduced to the Americas, highlighting the risk that additional pathogenic trematodes transmitted by the snail in its native range could be introduced to the United States. The current, possible human-infection risk in California clarifies the need to consider the introduced snail and its parasites from a public health perspective anywhere in the United States the snail has been introduced.

We report that 3 human-infecting trematodes and their introduced intermediate host snail are widespread in southern California freshwater fishing localities. Eating undercooked or underfrozen fish is the way people get infected by 2 of the parasite species, which are recognized as important human pathogens in other areas of the world. We also found 5 non­human-infectious trematodes carried by the snail that may be cointroduced, highlighting the possibility that other dangerous pathogens transmitted by the snail where it is native could arrive later or already be present in the United States. The common presence of the human-infecting fishborne trematodes at fishing localities, the widespread popularity of eating uncooked fish (eg, as sashimi, sushi, poke, or ceviche), and the potential for additional human-infecting trematodes to also be introduced, all justify consideration of the introduced snail and its parasites from a public health perspective in California and other areas in the United States where the parasites or the host snail have already been reported.

Regional Distribution of a Brain-Encysting Parasite Provides Insight on Parasite-Induced Host Behavioral Manipulation.

Some parasite species alter the behavior of intermediate hosts to promote transmission to the next host in the parasite's life cycle. This is the case for Euhaplorchis californiensis, a brain-encysting trematode parasite that causes behavioral changes in the California killifish (Fundulus parvipinnis). These manipulations increase predation by the parasite's final host, piscivorous marsh birds. The mechanisms by which E. californiensis achieves this manipulation remain poorly understood. As E. californiensis cysts reside on the surface of the killifish's brain, discerning regional differences in parasite distribution could indicate mechanisms for host control. In this study, we developed a method for repeated experimental infections. In addition, we measured brain-region specific density using a novel methodology to locate and quantify parasite infection. We show that E. californiensis cysts are non-randomly distributed on the fish brain, aggregating on the diencephalon/mesencephalon region (a brain area involved in controlling reproduction and stress coping) and the rhombencephalon (an area involved in controlling locomotion and basal physiology). Determining causal mechanisms behind this pattern of localization will guide future research examining the neurological mechanisms of parasite-induced host manipulation. These findings suggest that parasites are likely targeting the reproductive, monoaminergic, and locomotor systems to achieve host behavioral manipulation.

Metabolic theory of ecology successfully predicts distinct scaling of ectoparasite load on hosts.

The impacts of parasites on hosts and the role that parasites play in ecosystems must be underlain by the load of parasites in individual hosts. To help explain and predict parasite load across a broad range of species, quantitative theory has been developed based on fundamental relationships between organism size, temperature and metabolic rate. Here, we elaborate on an aspect of that 'scaling theory for parasitism', and test a previously unexplored prediction, using new data for total ectoparasite load from 263 wild birds of 42 species. We reveal that, despite the expected substantial variation in parasite load among individual hosts, (i) the theory successfully predicts the distinct increase of ectoparasite load with host body size, indicating the importance of geometric scaling constraints on access to host resources, (ii) ectoparasite load appears ultimately limited by access-not to host space-but to host energy, and (iii) there is a currency-dependent shift in taxonomic dominance of parasite load on larger birds. Hence, these results reveal a seemingly new macroecological pattern, underscore the utility of energy flux as a currency for parasitism and highlight the promise of using scaling theory to provide baseline expectations for parasite load for a diversity of host species.