Parasites and allergy: Observations from Africa

The majority of experiments investigating the immune response to gastrointestinal helminth infection use a single bolus infection. However, in situ individuals are repeatedly infected with low doses. Therefore, to model natural infection, mice were repeatedly infected (trickle infection) with low doses of Trichuris muris. Trickle infection resulted in the slow acquisition of immunity reflected by a gradual increase in worm burden followed by partial expulsion. Flow cytometry revealed that the CD4+ T cell response shifted from Th1 dominated to Th2 dominated, which coincided with an increase in Type 2 cytokines. The development of resistance following trickle infection was associated with increased worm expulsion effector mechanisms including goblet cell hyperplasia, Muc5ac production and increased epithelial cell turn over. Depletion of CD4+ T cells reversed resistance confirming their importance in protective immunity following trickle infection. In contrast, depletion of group 2 innate lymphoid cells did not alter protective immunity. T. muris trickle infection resulted in a dysbiotic mircrobiota which began to recover alpha diversity following the development of resistance. These data establish trickle infection as a robust and informative model for analysis of immunity to chronic intestinal helminth infection more akin to that observed under natural infection conditions and confirms the importance of CD4+ T cell adaptive immunity in host protection.

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Section: Resultsmentioning

confidence: 99%

Trickle infection and immunity to Trichuris muris

et al. 2019

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“…We found an inverse association between asthma and current infection with any helminths, particularly T. trichuria. However, the association between asthma and current infections in Africa has been inconsistent across studies (44). What was novel in this study is that we also collected data on history of using de-worming medication in the last 12 months.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for asthma among schoolchildren who participated in a case-control study in urban Uganda

Mpairwe

Namutebi

Nkurunungi

et al. 2019

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Methods Study designWe conducted a case-control study among schoolchildren, and report following STROBE guidelines (20). Study population, sampling and consentThe study was conducted in 5-17-year-old schoolchildren in primary and secondary schools in Wakiso District, Central Uganda, a predominantly urban setting.All schools in the study area were invited and 96% participated. At each school, we prescreened children by requesting all those with any breathing problems to register with us, and concurrently recruited two children without any breathing problems at random from the same class, using a random number generator programme in STATA (StataCorp, Texas, USA). The children delivered invitation letters to their parents; parents/guardians with telephones were invited to attend a meeting during which those interested provided written informed consent, and children aged ≥8 years provided written informed assent. Study enrollment was

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“…A number of studies suggest that individuals naturally infected by helminths have altered susceptibility to atopy and asthma when assessed by skin prick testing to common allergens (31–33). To determine whether T. muris trickle infection can alter the allergic response, T. muris infected mice were sensitized with the allergen OVA.…”

Section: Resultsmentioning

confidence: 99%

Trickle infection and immunity toTrichuris muris

Glover

Colombo

Thornton

et al. 2019

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13 The majority of experiments investigating the immune response to gastrointestinal helminth 14 infection use a single bolus infection. However, in situ individuals are repeatedly infected with low 15 doses. Therefore, to model natural infection, mice were repeatedly infected (trickle infection) with 16 low doses of Trichuris muris. Trickle infection resulted in the slow acquisition of immunity reflected 17 by a gradual increase in worm burden followed by a partial expulsion. Flow cytometry revealed 18 that the CD4+ T cell response shifted from Th1 dominated to Th2 dominated, which coincided 19 with an increase in Type 2 cytokines. The development of resistance following trickle infection 20 was associated with increased worm expulsion effector mechanisms including goblet cell 21 hyperplasia, Muc5ac production and increased epithelial cell turn over. Depletion of CD4+ T cells 22 reversed resistance confirming their importance in protective immunity following trickle infection. 23In contrast, depletion of group 2 innate lymphoid cells did not alter protective immunity. T. muris 24 trickle infection resulted in a dysbiotic mircrobiota which began to recover alpha diversity following 25 the development of resistance.26 These data support trickle infection as a robust and informative model for analysis of immunity to 27 chronic intestinal helminth infection more akin to that observed under natural infection conditions 28 and confirms the importance of CD4+ T cell adaptive immunity in host protection. 29 30 Author Summary 31 Infection with parasitic worms (helminths) is a considerable cause of morbidity in humans.32 Understanding how we respond to infection is crucial to developing novel therapies. Laboratory 33 models of helminth infection have been a valuable tool in understanding fundamental immune 34 responses to infection. However, typically an individual mouse will be infected with a large, single-35 dose of the parasite. This is in contrast to the natural scenario in which individuals will receive 36 frequent low level exposures. What is unknown is how repeated infection alters the development 37 of immunity to infection. We have developed a laboratory model to tackle this question. We 38 infected mice with the model helminth Trichuris muris on a weekly basis and assessed a range of 39 responses in comparison with a more traditional infection system. We found striking differences 40 in the dynamics of the infection, the host immune response, and in changes to host gut microbial 41 populations. Our study shows how resistance to helminth infection can develop over time in 42 response to repeat infection, and provides a model system that better reflects human immunity to 43 this parasite. 45 Introduction46 Gastrointestinal (GI) dwelling nematodes infect approximately 1 billion people worldwide causing 47 significant ill health (1). Prevalence is high in endemic areas although intensity of infection varies 3 48 with age, suggesting acquired immunity develops, although sterile immunity is rare and individuals 49 ar...

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Parasites and allergy: Observations from Africa

Cited by 18 publications

References 79 publications

Trickle infection and immunity to Trichuris muris

Trickle infection and immunity to Trichuris muris

Risk factors for asthma among schoolchildren who participated in a case-control study in urban Uganda

Trickle infection and immunity toTrichuris muris

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