domingo, 10 de outubro de 2010

Resposta imune no Intestino Quem entende?

Muito pouca entendida como resposta imune em meio a microflora e macroflora acontece Veja publicação do New England J of Medicine


Microflora, Helminths, and the Immune System — Who Controls Whom?

Achim Hoerauf, M.D.

N Engl J Med 363:1476-1478 | October 7, 2010

The gastrointestinal tract is the largest human immune organ. According to the classic view, it has evolved to control an immense biomass of foreign antigens, involving mechanisms for detecting and dispensing with dangerous pathogens while keeping “false alarms” to benign antigens, such as food, to a minimum. This balance is mediated by specialized immune-cell subgroups, including ?? T cells, M cells, and regulatory T cells. A recent study by Hayes and colleagues1 turns the view that the immune system controls gut flora inside out.

Hayes et al. carried out experiments using the rodent whipworm Trichuris muris, a worm that is similar to the human-infecting species T. trichiura. That both species elicit a response from type 2 helper T (Th2) cells in the large intestine supports the argument that T. muris infection in mice is a good model for T. trichiura infection in humans. Trichuris species infect many mammalian species, with an estimated 1 billion human infections by T. trichiura. These infections are associated with a lack of sanitation and thus poverty. Infection begins with the uptake of embryonated eggs. Larvae hatch in the colon, where they reside in the crypts of Lieberkühn and develop into adults, which mate and release unembryonated eggs with the feces into the environment.

After administering quinolones to mice to reduce their colonic flora, Hayes et al. introduced embryonated eggs of T. muris to the colons of these mice. They observed that fewer eggs hatched in the mice with depleted colonic flora. Further in vitro experiments showed that the attachment of enterobacteria to the polar opercula of the eggs was required for hatching and that the critical hatching factor in enterobacteria is the presence of fimbriae (short, fine, proteinaceous appendages that extend from the cell surface of gram-negative bacteria); eggs did not hatch in the presence of bacterial strains engineered to lack fimbriae.

The second and possibly even more interesting finding was that the antibiotic-induced depletion of intestinal microflora led not only to a reduction in the worm load but also to a shift in the T-cell–dependent immune response. Th2 responses were decreased, since fewer whipworms were binding to the intestinal walls, and responses by type 17 helper T (Th17) cells and regulatory T (Treg) cells were increased (Figure 1). This finding would not have been discovered without the presence of a Th2-inducing agent, such as worms. Perhaps this result is relevant to other Th2 inducers, such as food allergens, in which case the wisdom of consuming allergenic foods (e.g., lobster) while taking antibiotics could be questioned.

Figure 1

Hatching Parasites.

In summary, the work of Hayes et al. shows that the presence of microflora and macroflora (worms) shapes and controls the direction of immune reactions in the gut. The regulated network of gut flora has coevolved with humans, resulting in a symbiotic reciprocal control that achieves a balance in a healthy gut. The process of the synthesis and secretion of antimicrobial peptides by both the human host and the bacteria themselves is an example of this balance.2 The widespread use of antimicrobial peptides as food preservatives may shift this balance and may contribute to the increasing number of inflammatory bowel diseases. The use of nonsteroidal antiinflammatory drugs (NSAIDs) may also contribute to this imbalance, given suggestive evidence that these drugs exacerbate inflammatory bowel diseases.3

We should therefore continue to advocate for a restrictive use of NSAIDs, antibiotics, and food additives that will disturb microflora. We may also have to consider the implications of the work by Hayes et al. and that of other investigators4 when assessing the value of preoperative bowel decontamination, which might have implications for perioperative and postoperative immune reactions. We urgently need controlled studies on the consequences of antibiotic use for the shaping of immune reactions — to common antigens, for example. Such studies may provide a better understanding of the effect of the disturbance of gut flora on immune reactions.

Disclosure forms provided by the authors are available with the full text of this article at


KS Hayes, AJ Bancroft, M Goldrick, C Portsmouth, IS Roberts, RK GrencisExploitation of the intestinal microflora by the parasitic nematode Trichuris muris.Science2010;328:1391-1394
RE Hancock, HG SahlAntimicrobial and host-defense peptides as new anti-infective therapeutic strategies.Nat Biotechnol2006;24:1551-1557
H Kefalakes, TJ Stylianides, G Amanakis, G KoliosExacerbation of inflammatory bowel diseases associated with the use of nonsteroidal anti-inflammatory drugs: myth or reality?Eur J Clin Pharmacol2009;65:963-970
P Zapater, R Cano, L Llanos, Norfloxacin modulates the inflammatory response and directly affects neutrophils in patients with decompensated cirrhosis.Gastroenterology2009;137:1669-1679
Source Information

From the University Clinic, Bonn, Germany.
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