Microbiota regulates immune defense against respiratory tract influenza A virus infection

Abstract

Although commensal bacteria are crucial in maintaining immune homeostasis of the intestine, the role of commensal bacteria in immune responses at other mucosal surfaces remains less clear. Here, we show that commensal microbiota composition critically regulates the generation of virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection. By using various antibiotic treatments, we found that neomycin-sensitive bacteria are associated with the induction of productive immune responses in the lung. Local or distal injection of Toll-like receptor (TLR) ligands could rescue the immune impairment in the antibiotic-treated mice. Intact microbiota provided signals leading to the expression of mRNA for pro–IL-1β and pro–IL-18 at steady state. Following influenza virus infection, inflammasome activation led to migration of dendritic cells (DCs) from the lung to the draining lymph node and T-cell priming. Our results reveal the importance of commensal microbiota in regulating immunity in the respiratory mucosa through the proper activation of inflammasomes.

Disease tolerance and immunity in host protection against infection

“…The bacterial endosymbiont, Wolbachia, for example, enhances resistance to Drosophila C virus in flies 10,131 and to dengue and chikungunya virus infections in mosquitoes 132 ( Figure 5). Symbiotic interactions between bacteria and mice can also promote immune-driven resistance mechanisms against viral 133 , bacterial 134 or protozoan 135,136 infections ( Figure 5). This argues that the establishment of stable symbiotic interactions between microcellular and multicellular organisms is a widespread recurrent trait that modulates host resistance against a variety of pathogens ( Figure 5).…”

“…This protective effect has been linked to priming of the mosquito innate immune system and possibly competition for resources supporting pathogen replication. Symbiotic neomycin-sensitive bacteria can promote immune-driven resistance mechanisms against influenza A virus infection in mice, via mechanism involving bacterial sensing by inflammasomes 133 . The gut E. coli O86B7 commensal elicits an IgM antibody response directed against the galα(1,3)gal glycan that confers resistance to Plasmodium infection in mice and possibly in humans 135 while Lactobacillus and Bifidobacterium confer resistance to Plasmodium infection in mice via a mechanism that has not been clearly established 136 .…”

The regulation of host defences to infection by the microbiota

“…In addition to these distal signals, local microbes from the upper airway have also been demonstrated to regulate lower airway immunity 41, 65. It has been shown that mice maintained in specific pathogen‐free (SPF) conditions are more susceptible to influenza infection than those maintained in non‐SPF conditions 65.…”

“…The importance of host–microbiota interactions for our health has been highlighted by clinical studies and work with animal models demonstrating that microbiota dysbiosis is associated with diseases and immune dysfunctions in both intestinal and extra‐intestinal tissues. These include chronic inflammatory conditions in the intestine,31, 32 autoimmunity33, 34, 35 and increased susceptibility to intestinal and extra‐intestinal infections 15, 30, 32, 36, 37, 38, 39, 40, 41, 42, 43…”

A feasibility study: association between gut microbiota enterotype and antibody response to seasonal trivalent influenza vaccine in adults

“…Previous investigations have demonstrated a clear relationship between the gut microbiota and the protective antibody response to influenza in animal models,1, 2 and clinical studies also suggest the human gut microbiota influences the immune response 3, 4. This raises the possibility that an individual's gut microbiota may affect the strength of their immune response to vaccination.…”