Lack of interferon-γ confers impaired neutrophil granulocyte function and imparts prolonged survival of adult filarial worms in murine filariasis

Saeftel, Michael; Volkmann, Lars; Korten, Simone; Brattig, Norbert W.; Al-Qaoud, Khaled M.; Fleischer, Bernhard; Hoerauf, Achim

doi:10.1016/s1286-4579(01)01372-7

Cited by 56 publications

(69 citation statements)

References 55 publications

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“…IL-5 has been associated with both eosinophil-mediated (27) and neutrophil-mediated (3,52,53) killing of nematode parasites. Therefore, it is possible that in the S. stercoralis mouse model IL-5 is required for eosinophils and neutrophils in the innate response and for neutrophils in the adaptive response.…”

Section: Vol 74 2006 Eosinophils and Neutrophils In Protective Immumentioning

confidence: 99%

“…Neutrophils have also been associated, based on histological analyses, with killing larval Ancylostoma caninum in mice (59). Finally, mice deficient in gamma interferon and IL-5 have a defect in neutrophil function which results in increased survival of Litomosoides sigmodontis (3,52,53). Therefore, the alterations in parasite survival observed in naïve or immunized mice deficient in or depleted of IL-5 may ultimately be caused by a defect in either eosinophils or neutrophils.…”

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Role of Eosinophils and Neutrophils in Innate and Adaptive Protective Immunity to LarvalStrongyloides stercoralisin Mice

et al. 2006

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The goal of this study was to determine the roles of eosinophils and neutrophils in innate and adaptive protective immunity to larval Strongyloides stercoralis in mice. The experimental approach used was to treat mice with an anti-CCR3 monoclonal antibody to eliminate eosinophils or to use CXCR2 ؊/؊ mice, which have a severe neutrophil recruitment defect, and then determine the effect of the reduction or elimination of the particular cell type on larval killing. It was determined that eosinophils killed the S. stercoralis larvae in naïve mice, whereas these cells were not required for the accelerated killing of larvae in immunized mice. Experiments using CXCR2؊/؊ mice demonstrated that the reduction in recruitment of neutrophils resulted in significantly reduced innate and adaptive protective immunity. Protective antibody developed in the immunized CXCR2 ؊/؊ mice, thereby demonstrating that neutrophils were not required for the induction of the adaptive protective immune response. Moreover, transfer of neutrophil-enriched cell populations recovered from either wild-type or CXCR2؊/؊ mice into diffusion chambers containing larvae demonstrated that larval killing occurred with both cell populations when the diffusion chambers were implanted in immunized wild-type mice.

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Section: Vol 74 2006 Eosinophils and Neutrophils In Protective Immumentioning

confidence: 99%

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Role of Eosinophils and Neutrophils in Innate and Adaptive Protective Immunity to LarvalStrongyloides stercoralisin Mice

et al. 2006

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“…These observations showed that haematophagy was not accidental, but that L. sigmodontis ingests blood at specific periods of its development, thus raising a number of interesting questions. In the L. sigmodontis model major studies have been aimed at studying the role of immune factors in the regulation of the outcome of filarial infections (Allen et al 2000 ;Martin et al 2001 ;Saeftel et al 2001 ;Le Goff et al 2002 ;Babayan et al 2003Babayan et al , 2004Volkmann et al 2003). This study suggests that other factors, such as feeding habits and nutrition, may also have a role in development of the parasite and its success as a parasite, and thus provide a starting point for further investigations.…”

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Blood-feeding in the young adult filarial wormsLitomosoides sigmodontis

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Babayan

Hoerauf³

et al. 2004

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In this study with the filarial model Litomosoides sigmodontis, we demonstrate that the worms ingest host red blood cells at a precise moment of their life-cycle, immediately after the fourth moult. The red blood cells (RBC) were identified microscopically in live worms immobilized in PBS at 4 xC, and their density assessed. Two hosts were used : Mongolian gerbils, where microfilaraemia is high, and susceptible BALB/c mice with lower microfilaraemia. Gerbils were studied at 12 time-points, between day 9 post-inoculation (the worms were young 4th stage larvae) and day 330 p.i. (worms were old adults). Only the very young adult filarial worms had red blood cells in their gut. Haematophagy was observed between days 25 and 56 p.i. and peaked between day 28 and day 30 p.i. in female worms. In males, haematophagy was less frequent and intense. Similar kinetics of haematophagy were found in BALB/c mice, but frequency and intensity tended to be lower. Haematophagy seems useful to optimize adult maturation. These observations suggest that haematophagy is an important step in the life-cycle of L. sigmodontis. This hitherto undescribed phenomenon might be characteristic of other filarial species including human parasites.

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“…Recently, factors like IL-4, IL-5, and gamma interferon (IFN-␥) have been shown to be protective (5,28,34,38), and others, like NK cells, seem to promote the infection (3), probably through their cytokine production.…”

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B-Cell Deficiency Suppresses Vaccine-Induced Protection against Murine Filariasis but Does Not Increase the Recovery Rate for Primary Infection

et al. 2001

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To establish the role of B cells and antibodies in destroying filariae, mice lacking mature B cells and therefore unable to produce antibodies were used. Litomosoides sigmodontis offers a good opportunity for this study because it is the only filarial species that completes its life cycle in mice. Its development was compared in B-cell-deficient mice (BALB/c MT mice) and wild-type BALB/c mice in two different in vivo situations, vaccination with irradiated larvae and primary infection. In all cases, mice were challenged with subcutaneous inoculation of 40 infective larvae. Vaccine-induced protection was suppressed in B-cell-deficient mice. In these mice, eosinophils infiltrated the subcutaneous tissue normally during immunization; however, their morphological state did not change following challenge inoculation, whereas in wild-type mice the percentage of degranulated eosinophils was markedly increased. From this, it may be deduced that the eosinophil-antibody-B-cell complex is the effector mechanism of protection in vaccinated mice and that its action is fast and takes place in the subcutaneous tissue. In primary infection, the filarial survival and growth was not modified by the absence of B cells. However, no female worm had uterine microfilariae, nor did any mice develop a patent infection. In these mice, concentrations of type 1 (gamma interferon) and type 2 (interleukin-4 [IL-4], IL-5 and IL-10) cytokines in serum were lower and pleural neutrophils were more numerous. The effects of the MT mutation therefore differ from those in B1-cell-deficient mice described on the same BALB/c background, which reveal a higher filarial recovery rate and microfilaremia. This outlines B2-cell-dependent mechanisms as favorable to the late maturation of L. sigmodontis.Despite new chemotherapy protocols (30), filariae are still a major cause of serious tropical diseases (9, 35); therefore, it is worthwhile to consider a vaccination approach as a complementary measure. We now have a particularly relevant experimental model at our disposal with the rodent filaria Litomosoides sigmodontis. It is the only filarial species able to regularly develop from the infective larvae to the patent phase in the BALB/c mice (18,32). Therefore, the strength of this model is that is allows us to study and modulate the immune reaction during vaccination as well as during primary infection and thus to describe the immune mechanism critical for parasite control.

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Lack of interferon-γ confers impaired neutrophil granulocyte function and imparts prolonged survival of adult filarial worms in murine filariasis

Cited by 56 publications

References 55 publications

Role of Eosinophils and Neutrophils in Innate and Adaptive Protective Immunity to LarvalStrongyloides stercoralisin Mice

Role of Eosinophils and Neutrophils in Innate and Adaptive Protective Immunity to LarvalStrongyloides stercoralisin Mice

Blood-feeding in the young adult filarial wormsLitomosoides sigmodontis

B-Cell Deficiency Suppresses Vaccine-Induced Protection against Murine Filariasis but Does Not Increase the Recovery Rate for Primary Infection

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