Lethal LPS-independent side effects after microfilaricidal treatment in Acanthocheilonema viteae-infected rodents

Müller, Hermann; Zahner, Horst

doi:10.1007/s00436-005-1386-7

Cited by 4 publications

(1 citation statement)

References 25 publications

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“…Further, the Wolbachia surface protein WSP has been shown to induce IL-12 production by acting through TLR2 and -4 (4, 5). However, fatal effects mediated by microfilaria-derived components other than Wolbachia products have been demonstrated using filarial species that do not contain Wolbachia endosymbionts (29). In addition to direct stimulation of cytokine production by microfilariae or Wolbachia, it is also possible that the higher concentrations of IL-6, IL-12, TNF-␣, MCP-1, and MIP-1␣ observed in LPS-challenged mice infected with microfilariae were due to the elevated numbers of monocytes induced by the microfilaremia.…”

Section: Vol 76 2008 Sepsis In Helminth-infected Mice 1673mentioning

confidence: 99%

Microfilariae of the Filarial NematodeLitomosoides sigmodontisExacerbate the Course of Lipopolysaccharide-Induced Sepsis in Mice

et al. 2008

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Helminths facilitate their own survival by actively modulating the immune systems of their hosts. We investigated the impacts that different life cycle stages of the rodent filaria Litomosoides sigmodontis have on the inflammatory responses of mice injected with sublethal doses of lipopolysaccharide (LPS). Mice infected with female adult worms from prepatent infections, worms which have not yet started to release microfilariae, developed lower levels of proinflammatory cytokines in the peripheral blood after LPS challenge than shamtreated controls, demonstrating that female adult worms can mitigate the innate immune response. The presence of microfilariae in mice, however, through either direct injection or implantation of microfilariareleasing adult female worms, turned the LPS challenge fatal. This lethal outcome was characterized by increased plasma levels of gamma interferon (IFN-␥), tumor necrosis factor alpha (TNF-␣), interleukin 12 (IL-12), and IL-6, greater numbers of macrophages and granulocytes in the peripheral blood, and decreased body temperatures in microfilaria-infected mice. Microfilaria-infected mice deficient in IFN-␥ receptor and TNF receptor 1 had increased survival rates after LPS challenge compared to immune-competent mice, suggesting that microfilariae worsen LPS-induced sepsis through actions of IFN-␥ and TNF-␣. In summary, we have demonstrated that infection of mice with L. sigmodontis female adult worms from prepatent infections protects mice injected with LPS whereas microfilariae worsen LPS-induced sepsis through the induction of proinflammatory cytokines and upregulation of granulocytes, NK cells, and monocytes in the peripheral blood.Infections with helminths often cause chronic disease with a wide spectrum of clinical manifestations, ranging from asymptomatic to severe pathology. By actively suppressing the inflammatory responses of their hosts, helminths facilitate their own survival (26). This suppression will not only permit parasite persistence at high infection levels but also avoid pathological changes to the host. Amazingly, the presence of only one female adult worm of the rodent filarial nematode Litomosoides sigmodontis, an animal model for human filariasis (1, 18), is sufficient to prolong the viability of their progeny, the microfilariae, in the host (19). Although microfilariae given alone provoke a Th1 response in their hosts (25), adult filarial worms typically induce a Th2 immune response characterized by high levels of interleukin 4 (IL-4), IL-5, IL-10, IL-13, and immunoglobulin E as well as an augmentation of mast cells, eosinophils, and basophils (26).In addition, helminths induce a stage of hyporesponsiveness in their hosts (14), likely due to a targeted immune suppression by IL-10, transforming growth factor ␤, regulatory T cells, and alternatively activated macrophages (12,16,23,33,36,37). Recently, this immunomodulatory capacity of parasitic worms or their excretory/secretory products has been effectively utilized for therapeutic purposes in patients with inf...

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Section: Vol 76 2008 Sepsis In Helminth-infected Mice 1673mentioning

confidence: 99%