Innate immune response is our first line of defense against foreign bodies. For instance, when our bodies sense foreign microbes, we produce small proteins called Anti-microbial peptides (AMPs) that help trigger our first responder immune cells to mount a response. These cells detect the bacteria as non-self and jump into action to clear them away. All organisms armed with innate immunity have AMPs as part of their tool kit. AMPs are able to disrupt bacterial colonization and establishment by disrupting bacteria’s cell wall or interfering with the process of making new DNA and proteins. Although bacteria have become unpopular over the years due to their disease causing ability, there are millions of them that are essential to our development. For example, an earlier study found that germ free mice or mice born without any resident microbial population in their bodies have a poorly developed immune system including the inability to secrete AMPs. The authors of the current study want to understand if Apis mellifera, the African honey bee’s normal gut resident microbes have a role in triggering AMP production and if that is beneficial enough to fight infection caused by disease causing bacteria (1).
First, they test if AMPs are produced by honey bees by comparing the haemolymphs (blood equivalent in insects) obtained from honey bees that have been microbe free since birth with microbe free honeybees inoculated with a common type of honey bee gut microbe Snodgrassella alvis or with the digested guts of worker honeybees (which would contain normal microbial flora of honey bees). Out of the four common AMP classes produced by honeybees, apidaecin and hymenoptacein were found to be strongly induced in the haemolymph and intestinal lumen of the microbe exposed honeybees with apidaecin showing a 2.4fold increase in production. They suggest that apidaecin production in the haemolyph could trigger innate response of honey bees while their production in the gut lumen could modulate the gut microbial population to help respond to infections better. Next, they show that unlike the pathogenic E. coli bacteria, the resident microbial population is largely immune to the two forms of apidaecin. As mentioned above, this is important because bees have to fine tune AMP production so that it is selectively harmful to the invading pathogen while maintaining a good mix of the resident gut microbial population.
Finally, they test if AMP production could increase the survival chances of honey bees infected with E. coli. They infect germ free bees or bees inoculated with two different types of gut resident microbes (S. alvi and Gilliamella apicola) with E. coli and after a 3hr and 6hr interval, obtain haemolyph to check for how much of the injected E. coli was cleared as a result of the activation of first defense response triggered by AMP production. The bees that received inoculations of S. alvi and G. apicola were able to significantly clear out E. coli after 6hrs in two out of three trials. The second test they do is to check how long the bees survive post E. coli infection and in only two out of five total trials conducted, the gut microbe exposed bees were able to significantly increase their survival time. They suggest that this variability in trials show that having gut microbiota is not harmful to bees but can be useful in some instances to fight infection. It is indeed not ideal to get such a mix of outcomes in what was supposed to be their role defining experiment.
Why were some microbe free bees able to fight off E. coli as well as their gut microbe injected peers? They attribute it to seasonal differences and differences in the groups of bees used for the experiment which may very well have played a role in generating variability between trials. However, it is also possible that sustained AMP production and as a result better outcome for bees may require more than one type of gut resident microbe to be present. I also wondered if passage of immune response-eliciting proteins from the original mother bee to her eggs has a role in modulating immune response in the next generation. I am no bee research expert and this is just something I was thinking about while reading this paper. Passive adaptive immunity occurs in humans (and in other animals) where the mom is able to pass on germ fighting antibodies to babies during pregnancy, and after via breast feeding. Since bees do not make antibodies, other studies have shown that pieces of bacterial cells (dead or alive) from both disease causing and non-disease causing bacteria can be passed on via the eggs to the next generation, a phenomena called as trans-generational immune priming. What if these immune-eliciting bacterial proteins induce a response that is sufficient to tackle E. coli infection even in the absence of gut microbiota? Well, we will have to wait for the next research paper to add more weight to the proposed symbiotic relationship between bees and their gut bacteria in warding off infections.
Recently I began reading Ed Yong’s “I contain multitudes: The Microbes Within Us and a Grander View of Life”, a fascinating and superbly written book about animals’ intrinsic relationship with microbes that is beneficial at so many levels. Excellently researched, the book referenced a paper on how mouse specific and not human specific resident gut bacteria successfully induced a defense response in germ free mice infected with Salmonella (2). This study on bees shows how this relationship possibly extends to insects as well.