It can be hard to comprehend the damage that pathogenic viruses and microbes can inflict on the human body, especially if you have scientists prattling on about cells, using multi-syllabic acronyms and tossing around - god forbid! - actual numbers. It's helpful to have easily understood images to help put diseases into perspective, to understand that viruses like HIV have tangible and real effects. That's why I'm so happy to have stumbled upon an incredible image from a 2004 paper that is a pictorial testament to the immunological blitzkrieg that is HIV infection.
A well-known hallmark of HIV infection is the loss of lymphocytic CD4+ T-cells, otherwise known as "helper T-cells", that hunt and destroy invading bacteria, viruses and fungi. In this paper, the investigators were studying the underlying mechanisms that hasten the loss of these vital CD4+ T-cells from the gastrointestinal tract and the lymph nodes of HIV infected individuals.
Though we often think that the gastrointestinal tract has one job - to digest the meals that we organize our day around - it is, in fact, much more than just a digesting tube. The large intestine houses bacteria that produce vitamin K as well as a slew of water-soluble vitamins belonging to the B family, including folic acid, biotin and riboflavin. Serotonin factories in the stomach and small intestine, known as enterochromaffin cells, produce 90% of this vital neurotransmitter that modulates our emotions and moods, which might explain why a stomach bug can leave us emotionally depleted, why our stomach "flutters" with anxiety or love or why we might get a certain "gut instinct" about future events.
The intestine also houses immune cells in groups known as Peyer's patches that are sown along the tail-end of the GI tract known as the ileum, that abuts the large intestine. These cells lie in wait for that one moment when you go against your physician's recommendations and chow down on a microbe-laced ceviche on your vacation south of the equator. They serve as the "immune sensors of the intestine" (1). The gut has so many immune cells housed in its crevices - including at least 70% of the body's lymphocytes - that it is technically the body's largest lymphoid organ (1)!
In short, our intestine is not only the heart and soul of our body, but it is also its immunological epicenter. Perhaps we should consider being a little kinder to this spectacular wonder-organ.
Representative endoscopic photographs of the terminal ileum in the small intestine of a healthy patient on the left and a HIV-infected patient on the right. Arrows point to Peyer's patches, areas of lymphoid tissue housing CD4+ T-cells.
But back to this paper and this great image! On the left, we can see a snapshot of the ileum in a HIV-negative person. The endoscope - an expensive tube with a camera on its end exploring your nether regions - shows a rocky, Mars-like terrain in the ileum. This is healthy, all around A-plus stuff - those bumps scattered throughout are the Peyer's patches filled with immunological cells.
On the right, we see an incredibly smooth, denuded ileum in a HIV-positive individual. There are no lymphocytic bumps to be seen and the researchers attest to the subject's "almost complete absence of discernible lymphoid tissue" (2). In this patient, HIV has infected and destroyed many of the CD4+ cell clusters in the ileum. It's a rather grim sight; the difference between this HIV-infected ileum and the healthy one is striking in its austerity.
Now, a few caveats. These two pictures could be the only suitable images that the researchers found in both of the participants, though they do state that they are representative of their findings in all of the studied participants. But it could be the case that there exists ileum in healthy people that looks very much like our desolate AIDS ileum above, just as there could be ileum in AIDS patients that resemble pebbly, healthy ileum. Or these images could be confounded by age - younger individuals have far more Peyer's patches than older people - just another one of the innumerable upshots to getting old and wise (1). Or these pictures could represent just a momentary "snap shot" in time of a section of the gut whose immunological landscape is liable to change from week to week.
The researchers acknowledge that the images "could be considered anecdotal in isolation" but the endoscopic findings weren't an aberration. They found that certain CD4+ T-cells, bearing the very receptor that HIV uses to infect these cell, were preferentially depleted from the gastrointestinal tract; the frequency of these particular T-cells in the GI tract were far lower relative to other T-cells, indicating that HIV is selectively infecting and killing these cells and resulting in a diminished population in the gut. This depletion was only found in the GI tract, not in the blood or in other lymph nodes.
Other studies have confirmed this gut-focused assassination by the HIV virus, finding that HIV delivers a devastating blow to the immune system by killing up to 60% of CD4+ T-cells within 2 to 4 weeks of infection, and that this depletion can last for up to five years even with the use of retroviral therapy (3). HIV is truly a wrecking-ball of a virus, systematically destroying cells and tissues beginning with the very organ that takes such good care of us, physically and emotionally - our gut.
"Two brains are better than one". A great 2011 article from the New York Times on our "second brain", the gut and its nervous system. Check out The Other Brain Also Deals With Many Woes.
Find out more about Peyer's patches and their role in the intestine in this 2010 article, Peyer's Patches: The Immune Sensors of the Intestine.
(1) C. Jung et al. (2010) Peyer's Patches: The Immune Sensors of the Intestine. Int J Inflam. 2010: 823710.
(2) JM. Brenchley et al. (2004) CD4 T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract. J Exp Med. 200(6):749–759
(3) Evering TH et al (2012) Absence of HIV-1 Evolution in the Gut-Associated Lymphoid Tissue from Patients on Combination Antiviral Therapy Initiated during Primary Infection. PLoS Pathog. 8(2): e1002506.
Brenchley, J. (2004). CD4+ T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract Journal of Experimental Medicine, 200 (6), 749-759 DOI: 10.1084/jem.20040874