Secretory IgA molecules are the antibodies that help protect our intestines from pathogens. Researchers from ETH Zurich recently figured out how IgA combats these pathogens, and it’s not in a way that they expected.
Surprisingly, the IgA molecules effectively “chain” together bacterial cells as they are trying to divide. The chained bacteria can still multiply, but all of the daughter cells remain trapped by the IgA.
This chaining, or clumping, of bacteria isn’t a new phenomenon. Antibodies and bacteria clump together in a test tube, but researchers thought that this only occurred because the concentrations of bacteria and antibodies were so high that the two frequently contacted each other. This couldn’t be the case, however, because these same clumps have been observed in the intestine.
It turns out that these clumps can form even when the antibodies and bacteria are present at low concentrations and densities. The antibodies only have to trap a few bacteria to make a big impact. Once trapped, the antibodies don’t stop the bacteria from dividing, they simply chain all the daughter cells together! According to study author Wolf-Dietrich Hardt, “the clever thing about clump formation is that the antibodies don't kill the bacteria, which in the worst case could lead to a violent immune response. They simply prevent the microbes from interacting with the host, among themselves or with close relatives.”
In one experiment, the researchers gave mice an oral vaccine containing attenuated Salmonella typhimurium. Then, they infected the mice with 105 CFU of wild type S. typhimurium. The vaccine kept the bacteria from colonizing the mesenteric lymph nodes, invading cecal tissue, and producing intestinal inflammation. When they analyzed bacteria from the vaccinated mouse guts, S. typhimurium cells were coated with IgA and clumped together.
This clumping also limits the exchange of genetic information between different populations of bacteria in the intestine. The chained-up bacteria can’t make physical contact with other bacteria, so they aren’t able to take up antibiotic resistance genes, for example, from other pathogens.
To demonstrate this, the researchers co-infected the mice with bacteria that lacked a plasmid (a recipient strain) and bacteria that carried a plasmid (donor strain) that made the cells resistant to chloramphenicol. They found that the IgA chained up both the recipient and donor strains equally well. More importantly, vaccination decreased the rates of plasmid transfer from the donor to recipient cells.
These findings suggest that oral vaccines could be highly effective at preventing and treating intestinal diseases. The researchers at ETH Zurich think that these vaccines could be especially useful for vaccinating livestock, which are often reservoirs for antibiotic resistant pathogens.