Download Rapid environmental effects on gut nematode susceptibility in rewilded mice PDF

TitleRapid environmental effects on gut nematode susceptibility in rewilded mice
File Size5.1 MB
Total Pages28
Document Text Contents
Page 1


Rapid environmental effects on gut nematode

susceptibility in rewilded mice

Jacqueline M. Leung
1*, Sarah A. Budischak1, Hao Chung The2, Christina Hansen1,

Rowann Bowcutt
, Rebecca Neill

, Mitchell Shellman

, P’ng Loke

, Andrea L. Graham


1 Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United

States of America, 2 Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme,

Vo Van Kiet, Ho Chi Minh City, Viet Nam, 3 Department of Microbiology, New York University School of

Medicine, New York, New York, United States of America

* [email protected] (JML); [email protected] (ALG)


Genetic and environmental factors shape host susceptibility to infection, but how and how

rapidly environmental variation might alter the susceptibility of mammalian genotypes

remains unknown. Here, we investigate the impacts of seminatural environments upon the

nematode susceptibility profiles of inbred C57BL/6 mice. We hypothesized that natural

exposure to microbes might directly (e.g., via trophic interactions) or indirectly (e.g., via

microbe-induced immune responses) alter the hatching, growth, and survival of nematodes

in mice housed outdoors. We found that while C57BL/6 mice are resistant to high doses of

nematode (Trichuris muris) eggs under clean laboratory conditions, exposure to outdoor

environments significantly increased their susceptibility to infection, as evidenced by

increased worm burdens and worm biomass. Indeed, mice kept outdoors harbored as many

worms as signal transducer and activator of transcription 6 (STAT6) knockout mice, which

are genetically deficient in the type 2 immune response essential for clearing nematodes.

Using 16S ribosomal RNA sequencing of fecal samples, we discovered enhanced microbial

diversity and specific bacterial taxa predictive of nematode burden in outdoor mice. We also

observed decreased type 2 and increased type 1 immune responses in lamina propria and

mesenteric lymph node (MLN) cells from infected mice residing outdoors. Importantly, in our

experimental design, different groups of mice received nematode eggs either before or after

moving outdoors. This contrasting timing of rewilding revealed that enhanced hatching of

worms was not sufficient to explain the increased worm burdens; instead, microbial

enhancement and type 1 immune facilitation of worm growth and survival, as hypothesized,

were also necessary to explain our results. These findings demonstrate that environment

can rapidly and significantly shape gut microbial communities and mucosal responses to

nematode infections, leading to variation in parasite expulsion rates among genetically simi-

lar hosts.

PLOS Biology | March 8, 2018 1 / 28






Page 2

Page 14

Page 15

Page 27

46. Przyjalkowski Z. Effect of intestinal flora and of a monoculture of E. coli on the development of intestinal

and muscular Trichinella spiralis in mice. Bull Acad Pol Sci Biol. 1968; 16(7):433–7. PMID: 4884943.

47. Johnson J, Reid WM. Ascaridia galli (Nematoda): development and survival in gnotobiotic chickens.

Exp Parasitol. 1973; 33(1):95–9. PMID: 4632462.

48. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and repro-

ducibly alters the human gut microbiome. Nature. 2014; 505(7484):559–63.

nature12820 PMID: 24336217.

49. Dea-Ayuela MA, Rama-Iniguez S, Bolas-Fernandez F. Enhanced susceptibility to Trichuris muris infec-

tion of B10Br mice treated with the probiotic Lactobacillus casei. Int Immunopharmacol. 2008; 8(1):28–

35. PMID: 18068097.

50. Reynolds LA, Smith KA, Filbey KJ, Harcus Y, Hewitson JP, Redpath SA, et al. Commensal-pathogen

interactions in the intestinal tract: lactobacilli promote infection with, and are promoted by, helminth par-

asites. Gut Microbes. 2014; 5(4):522–32. PMID: 25144609.

51. Holm JB, Sorobetea D, Kiilerich P, Ramayo-Caldas Y, Estelle J, Ma T, et al. Chronic Trichuris muris

Infection Decreases Diversity of the Intestinal Microbiota and Concomitantly Increases the Abundance

of Lactobacilli. PLoS ONE. 2015; 10(5):e0125495. PMID:


52. Houlden A, Hayes KS, Bancroft AJ, Worthington JJ, Wang P, Grencis RK, et al. Chronic Trichuris muris

Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects

Reversed by Pathogen Clearance. PLoS ONE. 2015; 10(5):e0125945.

pone.0125945 PMID: 25938477.

53. Else KJ, Entwistle GM, Grencis RK. Correlations between worm burden and markers of Th1 and Th2

cell subset induction in an inbred strain of mouse infected with Trichuris muris. Parasite Immunol. 1993;

15(10):595–600. PMID: 7877836.

54. Shoham S, Levitz SM. The immune response to fungal infections. Br J Haematol. 2005; 129(5):569–82. PMID: 15916679.

55. Artis D, Potten CS, Else KJ, Finkelman FD, Grencis RK. Trichuris muris: host intestinal epithelial cell

hyperproliferation during chronic infection is regulated by interferon-gamma. Exp Parasitol. 1999; 92

(2):144–53. PMID: 10366539.

56. Dohms JE, Metz A. Stress—mechanisms of immunosuppression. Vet Immunol Immunopathol. 1991;

30(1):89–109. PMID: 1781159.

57. Antignano F, Mullaly SC, Burrows K, Zaph C. Trichuris muris infection: a model of type 2 immunity and

inflammation in the gut. J Vis Exp. 2011;(51). PMID: 21654621.

58. Cliffe LJ, Grencis RK. The Trichuris muris system: a paradigm of resistance and susceptibility to intesti-

nal nematode infection. Adv Parasitol. 2004; 57:255–307.

57004-5 PMID: 15504540.

59. Thomas MBB, S. Thermal biology in insect-parasite interactions. Trends Ecol Evol. 2003; 18(7):344–


60. Lazzaro BP, Flores HA, Lorigan JG, Yourth CP. Genotype-by-environment interactions and adaptation

to local temperature affect immunity and fecundity in Drosophila melanogaster. PLoS Pathog. 2008; 4

(3):e1000025. PMID: 18369474.

61. Fels D, Kaltz O. Temperature-dependent transmission and latency of Holospora undulata, a micronu-

cleus-specific parasite of the ciliate Paramecium caudatum. Proc Biol Sci. 2006; 273(1589):1031–8. PMID: 16627290.

62. Alto BW, Lounibos LP, Mores CN, Reiskind MH. Larval competition alters susceptibility of adult Aedes

mosquitoes to dengue infection. Proc Biol Sci. 2008; 275(1633):463–71.

2007.1497 PMID: 18077250.

63. Chase JM, Shulman RS. Wetland isolation facilitates larval mosquito density through the reduction of

predators. Ecol Entomol. 2009; 34(6).

64. Orsted M, Schou MF, Kristensen TN. Biotic and abiotic factors investigated in two Drosophila species—

evidence of both negative and positive effects of interactions on performance. Sci Rep. 2017; 7:40132. PMID: 28059144.

65. Little TJ, Colegrave N. Caging and Uncaging Genetics. PLoS Biol. 2016; 14(7):e1002525. https://doi.

org/10.1371/journal.pbio.1002525 PMID: 27458971.

66. Maizels RM, Nussey DH. Into the wild: digging at immunology’s evolutionary roots. Nat Immunol. 2013;

14(9):879–83. PMID: 23959175.

67. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source

platform for biological-image analysis. Nat Methods. 2012; 9(7):676–82.

2019 PMID: 22743772.

Environmental effects on worm susceptibility in mice

PLOS Biology | March 8, 2018 27 / 28

Page 28

Similer Documents