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Understanding the primary literature: Interactions between bacteria and the immune system.
Don’t you wish you could understand primary literature? After all, this is where important scientific discoveries are published, right? This post breaks down a complex scientific paper published in the Journal of Immunology, and explains the gist of the authors’ findings; hidden within the language of the immunologists is a vast wealth of interesting information!
Just to make a point, let’s start with the title. “Reciprocal Interactions between Commensal Bacteria and gd Intraepithelial Lymphocytes during Mucosal Injury”. The point – there’s no need to be intimidated. Here’s a list of terms to help us decifer the meaning of this phrase:
- “Commensal bacteria” refers to the relationship of bacteria to our large intestine, where they live and benefit from the environment, without causing harm to the intestine itself. In fact, science is discovering a plethora of positive roles for these inhabitants.
- “gd Intraepithelial Lymphocytes”, or IEL, are simply a class of immune cells that are situated in the intestinal wall. From now on, I will refer to them only as immune cells, to avoid confusion. The authors of this paper describe the interactions of these cells with the commensal bacteria already present in the large intestine.
- “Mucosal” is a term used here to describe the mucous layer surrounding the lumen of the large intestine, or colon (I will use “intestine” and “colon” interchangeably here).
**I included the title section in order to convince readers that it is possible to read the primary literature accurately, while removing the jargon.
I’ve broken down the background information you’ll need to know in order to understand what the authors of this paper sought out to do:
- Did you know that even your intestine has an immune system? The intestinal immune system has coevolved with a vast number of home-grown bacteria, which, as long as they remain confined within the intestinal lumen, do not post a significant threat to human health.
- However, should the intestinal mucous layer become injured by environmental factors, such as toxins, the body is rendered susceptible to opportunistic invasion by the home-grown, or commensal, bacteria.
- The authors note that analysis of mice lacking immune cells in the intestine revealed that those cells promote repair of injured intestinal mucosa.
- The molecular details of the cellular immune response to intestinal injury are poorly understood, and little is known about the factors that regulate this response.
Objective: To uncover new insights into the role of intestinal immune cells in maintaining intestinal homeostasis, or stability, following mucosal injury.
**While the authors performed a series of experiments relating to this objective, they highlight three novel findings in both the introduction and conclusion of this publication, and these are described here.
1. The authors use DNA microarray technology, essentially a visual depiction of a cell’s gene expression pattern (see picture for an example), to analyze the expression pattern in intestinal immune cells.
Rationale: Since previous studies have shown that intestinal immune cells play a unique role in tissue repair, the authors hypothesized that this was representative of a more complex response to tissue damage.
Experimental Design: To test this idea, the authors used DNA microarrays to view the intestinal immune cells’ genetic response to damage. This was done using a mouse model of colonic mucosal injury; treatment of these mice with dextran sodium sulfate (DSS) results in colon-specific mucosal damage.
Results: Comparison of the DSS-treated and –untreated microarray expression profiles revealed a complex intestinal immune cell response to damage; expression of 272 genes was altered 2-fold or more in intestinal immune cells isolated from DSS-treated mice. Of these, the authors observed enhanced expression of genes encoding factors that provide protection to cells against harmful agents. A large proportion of DSS-induced changes occurred in genes involved in inflammation, as well as genes involved in the initial immune response to bacteria, and directly bacteriocidal components.
2. The authors found that commensal bacteria direct some of these intestinal immune cell responses to mucosal injury.
Rationale: Several studies have revealed that bacteria are known to govern many key functions of mucosal cells; however, there have been no studies addressing the role of indigenous intestinal bacterial. Thus, the authors sought to test the hypothesis that indigenous intestinal bacteria govern elements of the intestinal immune cell injury response.
Experimental Design: The authors proceeded to test this hypothesis by assessing the complex DSS-induced gene expression program in germfree mice, by DNA microarray. Germfree mice are exactly as they appear to be; germ free. The mice are bred and raised in isolation, such that they are not exposed to bacteria, and therefore have none living in their intestine. The list of 272 DSS-regulated genes identified by the conventional analysis was used to recover the signal intensities for these genes from the germfree microarray dataset.
Results: Commensal bacteria were required for DSS-induced expression of a subset of genes involved in protecting the cell from harm. The authors were surprised to find that the bacteria were also required for DSS-induced expression of the majority of the genes known to cause inflammation.
3. Finally, the authors find that intestinal immune cells limit opportunistic penetration of commensal bacteria immediately following mucosal injury. Recall that, should the intestinal mucous layer become injured by environmental factors, such as toxins, the body is rendered susceptible to opportunistic invasion by the home-grown, or commensal, bacteria.
Rationale: Since, the intestinal immune cells are ideally situated to sense penetration of the mucosa by commensal bacteria, the authors hypothesized that intestinal immune cells may play a role in limiting opportunistic penetration of commensals across damaged mucosal surfaces.
Experimental Design: To test this idea, the authors compared numbers of mucosa-penetrant commensal bacteria in normal mice, and in mice genetically engineered to lack intestinal immune cells (meaning that the gene required to produce those cells is deleted), following DSS-induced colonic injury.
Results: Numbers of mucosa-penetrant bacteria recovered from mice lacking intestinal immune cells were significantly higher than in normal mice after three days of treatment. The authors found no significant differences in the numbers of mucosa-penetrant bacteria before three days of DSS treatment, suggesting that blatant damage to the intestinal mucosa is necessary for bacterial penetration.
The authors demonstrated that intestinal immune cells mount a complex response to mucosal injury, and that commensal bacteria direct key elements of this response, including expression of genes that cause inflammation, and those that directly kill bacteria. Futhermore, they have shown that intestinal immune cells may play a role in controlling opportunistic penetration of commensal bacterial immediately following damage.
What does it all mean?
This study demonstrates that intestinal immune cells communicate with commensal bacteria, which signal to intestinal immune cells by directing the genetic response of the cells following mucosal injury. At the same time, intestinal immune cells defend against opportunistic invasion by commensals, immediately following damage; thus, intestinal immune cells make multifaceted contributions to maintaining homeostasis after damage to the intestinal mucous lining.
Not so bad, was it?