Abstract
The intestinal microbiota are pivotal in determining the developmental, metabolic and immunological status of the mammalian host. However, the intestinal tract may also accommodate pathogenic organisms, including helminth parasites which are highly prevalent in most tropical countries. Both microbes and helminths must evade or manipulate the host immune system to reside in the intestinal environment, yet whether they influence each other’s persistence in the host remains unknown. We now show that abundance of Lactobacillus bacteria correlates positively with infection with the mouse intestinal nematode parasite, Heligmosomoides polygyrus, as well as with heightened regulatory T cell (Treg) and Th17 responses. Moreover, H. polygyrus raises Lactobacillus species abundance in the duodenum of C57BL/6 mice, which are highly susceptible to H. polygyrus infection, but not in BALB/c mice, which are relatively resistant. Sequencing of samples at the bacterial gyrB locus identified the principal Lactobacillus species as L. taiwanensis, a previously characterized rodent commensal. Experimental administration of L. taiwanensis to BALB/c mice elevates regulatory T cell frequencies and results in greater helminth establishment, demonstrating a causal relationship in which commensal bacteria promote infection with an intestinal parasite and implicating a bacterially-induced expansion of Tregs as a mechanism of greater helminth susceptibility. The discovery of this tripartite interaction between host, bacteria and parasite has important implications for both antibiotic and anthelmintic use in endemic human populations.
Highlights
In both humans and mice, the intestinal microbiota are essential for development of a mature immune system, and for maintaining immunological homeostasis in the intestinal tract.[1-4]
The role of the intestinal microbiota in susceptibility to pathogen infection can be studied in GF mice; it is difficult to ascertain whether differences in the ability to clear infections are due to an abnormally-developed immune system, differences in intestinal physiology, or to the absence of bacteria that may alter the immune response or physiology of the host at the time of infection
Examining the composition of the fecal microbiota following vancomycin treatment revealed an elevated abundance of members of the Lactobacillaceae and Enterobacteriaceae families and reduced abundance of Eubacterium/Clostridium species (Fig. 1D–F), leading us to hypothesize that altered levels of these bacterial groups affected H. polygyrus survival
Summary
In both humans and mice, the intestinal microbiota are essential for development of a mature immune system, and for maintaining immunological homeostasis in the intestinal tract.[1-4]. The presence or absence of specific species of bacteria within the microbiota can be instrumental in driving immunological differentiation in the intestinal tract. Germ-free (GF) mice raised in the absence of commensal microbes show impaired immunological development,[14] and a systemic skewing toward Th2 responses.[15,16]. While GF mice are generally more susceptible to infections with bacterial or viral agents,[14] persistence of the gastrointestinal helminth parasite Heligmosomoides polygyrus is markedly reduced in these animals compared with conventionally raised mice.[17-19]. As the outcome of H. polygyrus infection is likely dependent on the immediate cytokine environment,[20-22] we postulated that the composition of the microbiota may alter the priming of the murine immune system to alter susceptibility to helminth infection
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