Identification of Mamu-DRB1 gene as a susceptibility factor for Entamoeba nuttalli infection in Chinese Macaca mulatta

Highlights

• Analysis of 76 stool samples from rhesus macaques in two provinces of China.

• High prevalent (69.23%) of Entamoeba nuttalli in Mount Qing-ling's macaques

• Sequence of Mamu-DRB1, Mamu-DPB and Mamu-B genes in these macaques

• Mamu-DRB1 genes were highly polymorphic in Mount Qian-ling and Long-hu's macaques

• Mamu-DRB1, not Mamu-DPB or Mamu-B gene, was related to E. nuttalli infection.

Abstract

Entamoeba nuttalli infection is highly prevalent in captive and wild macaques. A recent study suggested that the genetic factor of host macaques was correlated with the genotypes of E. nuttalli isolates. This study focused on the correlation between the rhesus macaque host major histocompatibility complex gene and E. nuttalli infection. Thirty-nine stool samples were obtained from Mount Qing-ling (Guizhou Province, China). Polymerase chain reaction analysis detected the infection rate of E. nuttalli, Entamoeba coli, and Entamoeba chattoni as 69.23%, 69.23%, and 87.18%, respectively. A new Serine-rich Protein genotype was detected, and the rRNA of E. nuttalli isolates from Mount Qian-ling was completely identical to the GY4 strain. In the distance-based neighbor-joining tree, Mamu-DRB1, not Mamu-DPB or Mamu-B gene, was related to E. nuttalli infection. Mamu-DRB1 genes of rhesus macaques in Mounts Qian-ling and Long-hu were highly polymorphic, and the rhesus macaques with two major types of Mamu-DRB1 showed susceptibility to E. nuttalli infection. The Mamu-DRB1 gene analysis in this study indicated that the Mamu-DRB1 gene is an important factor that influences the susceptibility of E. nuttalli infection in Chinese Macaca mulatta. This study contributes to a better understanding of host susceptibility to Entamoeba.

Introduction

Entamoeba nuttalli, an amoeba species isolated from macaques, phylogenetically located more closely related to Entamoeba histolytica, has been recently detected in both non-human primates and humans (Feng et al., 2014; Levecke et al., 2015; Tachibana et al., 2016), which may result in liver abscess, hemorrhagic dysentery, or other extraintestinal pathologies and even death(Levecke et al., 2015). Most E. nuttalli infected non-human primates, and the liver abscess in pathological manifestations was similar to E. histolytica (Guan et al., 2018). No study, however, has confirmed the reason why E. nuttalli infected macaques instead of humans.

E. nuttalli and E. histolytica have been misidentified in routine inspections due to their similar morphology but are now considered separate species with restricted host specificity (Tachibana et al., 2013). Different species of Entamoeba may have different hosts, and the host of E. histolytica is mainly humans, supplemented by monkeys. Hosts of Entamoeba dispar and E. nuttalli are mainly monkeys and humans and mainly monkeys, respectively (Tachibana et al., 2013). Entamoeba polecki is divided into four subtypes with high genetic similarity, but each subtype has its specific host. It is speculated that E. polecki is influenced by different hosts and differentiated into different subtypes (Regan et al., 2014). Among these subtypes, E. polecki is from swine, Entamoeba chattoni is from monkeys, and the isolate from ostriches represents subtypes ST1, ST2, and ST3(Stensvold et al., 2011). E. polecki ST4 is restricted to humans and unlikely to be zoonotic(Stensvold et al., 2018). The host susceptibility of Entamoeba is worth exploring.

E. nuttalli and E. histolytica have similar pathogenic genes and biological characteristics but have different suitable hosts(Tachibana et al., 2013). Previous studies have shown that the genetic distance of the major histocompatibility complex (MHC) gene in macaques is positively correlated with the genetic distance of the infected E. nuttalli gene (Wei et al., 2018). In many studies, host genetic diversity has been considered a critical factor affecting pathogen genetic diversity(Dimitrov et al., 2015). In the genetic evolution of parasites, adaptation to host MHC is an important part of parasite immune evasion (Debierre-Grockiego et al., 2009; Goncalves et al., 2013). The polymorphism of macaque MHC is strong, and many studies have shown that macaque MHC is related to the susceptibility of parasites. Therefore, given that more information is advantageous in studying factors contributing to the susceptibility of E. nuttalli, this study aimed to detect the correlation between the rhesus macaque host MHC gene and E. nuttalli infection in Mount Qian-ling (Guizhou Province, China). The genetic polymorphism of Mamu-DRB1, Mamu-DPB, and Mamu-B genes of rhesus macaques was analyzed.