Despite that finding, Dr. Kern said that the major question should not be whether fungi or bacteria are the central players. Rather, attention should be turned to problems with the nasal mucosal immune barrier of CRS patients.
Explore this issue:June 2009
Remember that staph and fungi are very common, he said. They’re frequently recovered from both normal and CRS patients. It’s inflammation as well, not tissue invasion. So the assumption that we’re making is that microbial pathogens are key to the whole process. I have some problems with that. Rather than debate what the organism is, we should be looking at the host, because it’s really a dysfunctional host- environment interaction. And the key problem is the host, not the bacteria.
The research team at Northwestern, focusing on chronic rhinosinusitis with polyps, examined defects in epithelial integrity and repair, defects in toll receptor signaling, and defects in the transition from an innate response to an acquired response.
When looking at the integrity of the epithelium, they screened a great number of genes. Thus far, we have identified four that seem to be part of the problem: three genes in the S100 group, which are important in repair and also have antimicrobial effects; and Spink 5, a protease inhibitor.
The epithelial cells in sinusitis with polyps are deficient in Spink 5, so they would have a decreased ability to limit or mute the protease effects of fungi or bacteria, which mediates their ability to dissolve the epithelial barrier, Dr. Kern said.
As for S100’s role, he said, If they’re diminished, that would certainly foster colonization of bacteria. So if patients with polypoid sinusitis have this defect, this would lead to slower healing following injury as well as increased microbial colonization. These effects are superimposed on the fragile mechanical barrier mediated by diminished Spink 5, he said.
In looking at pattern-recognition receptor signaling, researchers focused on the TLR-2 because it has been associated with staph and fungi. Northwestern researchers exposed epithelial cells to TLR-2 ligands and assayed for cytokines responses. They saw that the IL-8 response was diminished, causing a muted ability to recruit neutrophils as well an enhanced tendency to generate IL-6.
What does this mean? We’re not certain. But if you think about this CRS-with-polyps phenotype, there’s a diminished innate immune response, so this IL-8 would follow into that, Dr. Kern said. On the other hand, one of things that IL-6 does is just that: It shuts off the innate immune response and fosters the acquired immune response. So the combined effect of defects in this pathway could theoretically foster the picture of diminished innate immunity coupled with an enhanced acquired immune response-the picture we see in nasal polyposis.