Transcriptome variation in response to gastrointestinal nematode infection in goats

Abstract

Gastrointestinal nematodes (GIN) are a major constraint for small ruminant production. Due to the rise of anthelmintic resistance throughout the world, alternative control strategies are needed. The development of GIN resistance breeding programs is a promising strategy. However, a better understanding of the mechanisms underlying genetic resistance might lead to more effective breeding programmes. In this study, we compare transcriptome profiling of abomasal mucosa and lymph node tissues from non-infected, resistant and susceptible infected Creole goats using RNA-sequencing. A total of 24 kids, 12 susceptible and 12 GIN resistant based on the estimated breeding value, were infected twice with 10,000 L3 Haemonchus contortus. Physiological and parasitological parameters were monitored during infection. Seven weeks after the second infection, extreme kids (n = 6 resistant and 6 susceptible), chosen on the basis of the fecal egg counts (FEC), and 3 uninfected control animals were slaughtered. Susceptible kids had significantly higher FEC compared with resistant kids during the second infection with no differences in worm burden, male and female worm count or establishment rate. A higher number of differentially expressed genes (DEG) were identified in infected compared with non-infected animals in both abomasal mucosa (792 DEG) and lymph nodes (1726 DEG). There were fewer DEG in resistant versus susceptible groups (342 and 450 DEG, in abomasal mucosa and lymph nodes respectively). 'Cell cycle' and 'cell death and survival' were the main identified networks in mucosal tissue when comparing infected versus non-infected kids. Antigen processing and presentation of peptide antigen via major histocompatibility complex class I were in the top biological functions for the DEG identified in lymph nodes. The TGFβ1 gene was one of the top 5 upstream DEG in mucosal tissue. Our results are one of the fist investigating differences in the expression profile induced by GIN infection in goats.

Fig 1. Experimental design.

S, susceptible; R, resistant; Non, non-infected.

Fig 2. Least square means of fecal egg counts (FEC) and packed cell volume (PCV) in resistant (r) and susceptible (s) Creole kids infected with 10,000 H. contortus larvae (L3) and non-infected (n) animals.

(a) first infection, (b) second infection.

Fig 3. Top 5 biological processes that changed among groups.

Infected versus non-infected (Inf. vs non-inf.), resistant versus susceptible (Res. vs sus.).

Fig 4. Top 5 cellular components and molecular functions that changed among groups.

Infected versus non-infected (Inf. vs non-inf.), resistant versus susceptible (Res. vs sus.).

Fig 5. Top 5 diseases and biological function identified by Ingenuity pathway analysis using DE genes.

Fig 6. Genes controlling cell survival that were differently expressed in infected versus non-infected mucosal tissue.

Fig 7. Genes controlling cell survival that were differently expressed in resistant versus susceptible mucosal tissue.

Fig 8. Comparison of fold changes of deferentially expressed genes measured by RNA-Seq (black) and qPCR analyses (white) according to the groups (resistant vs. susceptible, R/S and infected vs. non-infected, I/NI) and the tissues (mucosa and lymph nodes).