We have come a long way in our understanding how exactly pathogenic bacteria can invade and populate the gut. Yet, there still remains uncertainty as to how exactly our immune system responds to and eliminates these infectious bacteria. A recent study addressed this by investigating the immune response to pathogenic bacteria in mice guts.
Some Escherichia coli can be pathogenic and infect the human gastrointestinal tract. In these instances, these Gram-negative bacteria attach to and populate the gut and cause lesions to the epithelium through a well-characterized attaching-and-effacing behavior. It is currently understood that IgG antibodies are produced in response to E. coli infection, but the exact cellular underpinnings as to how the bacteria are eliminated are unknown.
To model this, researchers infected germ free mice with Citrobacter rodentium, a bacterial strain known to carry genes that exhibits effacement pathology in mice. The specific genes of interest that induce enterocyte effacement (LEE) are referred to as a pathogenicity island, loci responsible for virulent behavior, and they are present in both E. Coli and C. rodentium. The researchers measured adaptive immunity reaction in response to C. rodentium infection, and specifically looked to see if LEE - the virulent bacterial signature - was down-regulated.
It was found that the LEE virulent strain was down-regulated concomitant to an increase in release of IgG antibodies. These IgG antibodies were found to be specific to the LEE virulent expression, as supported by significant IgG binding affinity to the virulent strain. The IgG antibodies eliminated the specific C. rodentium phenotype that expressed the LEE loci, and upon binding to the bacteria, they were removed by neutrophils.
Interestingly, the C. rodentium avirulent phenotype that lacked the LEE was not eliminated by IgG antibodies. However, these bacteria were subsequently outcompeted by other microbiota populations. Together, this information suggests that IgG could selectively eliminate the C. rodentium virulent phenotype, and innate immunity could eventually remove the non-virulent populations.
This study provides excellent insight into how our immune system can distinguish between good and bad bacteria in addition to describing the underlying cellular mechanism. Defining the molecular underpinnings of antibody action will allow us to make significant advancements in therapeutic approach. Understanding the molecular pathways is a critical first step toward pharmacotherapeutic intervention, and this study could potentially lead to the development of some exciting advancements in the future.