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Susceptibility to Ticks and Lyme Disease Spirochetes Is Not Affected in Mice Coinfected with Nematodes.

Maaz D, Rausch S, Richter D, Krücken J, Kühl AA, Demeler J, Blümke J, Matuschka FR, von Samson-Himmelstjerna G, Hartmann S - Infect. Immun. (2016)

Bottom Line: In a parasitological survey of wild mice in Berlin, Germany, approximately 40% of Ixodes ricinus-infested animals simultaneously harbored a nematode of the genus Heligmosomoides We therefore aimed to analyze the immunological impact of the nematode/tick coinfection as well as its effect on the tick-borne pathogen Borrelia afzelii Hosts experimentally coinfected with Heligmosomoides polygyrus and larval/nymphal I. ricinus ticks developed substantially stronger systemic type 2 T helper cell (Th2) responses, on the basis of the levels of GATA-3 and interleukin-13 expression, than mice infected with a single pathogen.During repeated larval infestations, however, anti-tick Th2 reactivity and an observed partial immunity to tick feeding were unaffected by concurrent nematode infections.Importantly, the strong systemic Th2 immune response in coinfected mice did not affect susceptibility to tick-borne B. afzelii An observed trend for decreased local and systemic Th1 reactivity against B. afzelii in coinfected mice did not result in a higher spirochete burden, nor did it facilitate bacterial dissemination or induce signs of immunopathology.

View Article: PubMed Central - PubMed

Affiliation: Institute of Immunology, Centre of Infection Medicine, Freie Universität Berlin, Berlin, Germany Institute of Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.

No MeSH data available.


Related in: MedlinePlus

Kinetics of GATA-3+ CD4+ Th2 cells from C57BL/6 mice during infestation with I. ricinus ticks alone and during infestation with I. ricinus ticks and coinfection with H. polygyrus. (A) Experimental setup showing the time line (in days) of exposure to H. polygyrus (H.p.) and to I. ricinus (I.r.) larvae and blood collection. (B) Representative flow cytometry density plots of peripheral blood CD4+ cells stained for Foxp3 and GATA-3 on day 13. (C, D) Frequencies of GATA-3+ (C) and Foxp3+ (D) CD4+ cells (mean ± SD) in the peripheral blood of H. polygyrus-infected mice (left), I. ricinus-infested mice (middle), and H. polygyrus- and I. ricinus-coinfected mice (right) normalized to those in the peripheral blood of naive controls. Gray shading and vertical lines, period of larval tick feeding and the day of dissection, respectively. One-way ANOVAs with a Bonferroni-corrected pairwise t test were performed for every time point in the kinetic analysis. d, day. (E) Number of adult H. polygyrus worms isolated from small intestines on day 41. The box plot shows the medians and quartiles, with whiskers indicating 95% CIs. Differences were tested using an unpaired t test. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant. Data are for 5 or 6 mice per group.
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Figure 3: Kinetics of GATA-3+ CD4+ Th2 cells from C57BL/6 mice during infestation with I. ricinus ticks alone and during infestation with I. ricinus ticks and coinfection with H. polygyrus. (A) Experimental setup showing the time line (in days) of exposure to H. polygyrus (H.p.) and to I. ricinus (I.r.) larvae and blood collection. (B) Representative flow cytometry density plots of peripheral blood CD4+ cells stained for Foxp3 and GATA-3 on day 13. (C, D) Frequencies of GATA-3+ (C) and Foxp3+ (D) CD4+ cells (mean ± SD) in the peripheral blood of H. polygyrus-infected mice (left), I. ricinus-infested mice (middle), and H. polygyrus- and I. ricinus-coinfected mice (right) normalized to those in the peripheral blood of naive controls. Gray shading and vertical lines, period of larval tick feeding and the day of dissection, respectively. One-way ANOVAs with a Bonferroni-corrected pairwise t test were performed for every time point in the kinetic analysis. d, day. (E) Number of adult H. polygyrus worms isolated from small intestines on day 41. The box plot shows the medians and quartiles, with whiskers indicating 95% CIs. Differences were tested using an unpaired t test. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant. Data are for 5 or 6 mice per group.

Mentions: GraphPad Prism (version 5.01) software (San Diego, CA, USA) was used for the plotting and statistical analysis of the experimental infection data. The data were tested for statistically significant differences using an unpaired t test, one-way analysis of variance (ANOVA) with a Bonferroni-corrected posttest (see Fig. 3 and 5), and two-way-ANOVA (see Fig. 2) under the assumption of a normal distribution of the FACS fluorescence data, ELISA optical density data, and the majority of the experimental parasite infection data. The posttests following the two-way ANOVA for individual pairs using the Bonferroni correction were performed with the posttest calculator (GraphPad Software). The number of engorged tick nymphs and the molting rate in Fig. 7A and D, respectively, and the cell counts in Fig. S1B in the supplemental material were not normally distributed, and differences were tested using the Mann-Whitney U test. Differences with P values below 0.05 were considered to be significant.


Susceptibility to Ticks and Lyme Disease Spirochetes Is Not Affected in Mice Coinfected with Nematodes.

Maaz D, Rausch S, Richter D, Krücken J, Kühl AA, Demeler J, Blümke J, Matuschka FR, von Samson-Himmelstjerna G, Hartmann S - Infect. Immun. (2016)

Kinetics of GATA-3+ CD4+ Th2 cells from C57BL/6 mice during infestation with I. ricinus ticks alone and during infestation with I. ricinus ticks and coinfection with H. polygyrus. (A) Experimental setup showing the time line (in days) of exposure to H. polygyrus (H.p.) and to I. ricinus (I.r.) larvae and blood collection. (B) Representative flow cytometry density plots of peripheral blood CD4+ cells stained for Foxp3 and GATA-3 on day 13. (C, D) Frequencies of GATA-3+ (C) and Foxp3+ (D) CD4+ cells (mean ± SD) in the peripheral blood of H. polygyrus-infected mice (left), I. ricinus-infested mice (middle), and H. polygyrus- and I. ricinus-coinfected mice (right) normalized to those in the peripheral blood of naive controls. Gray shading and vertical lines, period of larval tick feeding and the day of dissection, respectively. One-way ANOVAs with a Bonferroni-corrected pairwise t test were performed for every time point in the kinetic analysis. d, day. (E) Number of adult H. polygyrus worms isolated from small intestines on day 41. The box plot shows the medians and quartiles, with whiskers indicating 95% CIs. Differences were tested using an unpaired t test. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant. Data are for 5 or 6 mice per group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4862734&req=5

Figure 3: Kinetics of GATA-3+ CD4+ Th2 cells from C57BL/6 mice during infestation with I. ricinus ticks alone and during infestation with I. ricinus ticks and coinfection with H. polygyrus. (A) Experimental setup showing the time line (in days) of exposure to H. polygyrus (H.p.) and to I. ricinus (I.r.) larvae and blood collection. (B) Representative flow cytometry density plots of peripheral blood CD4+ cells stained for Foxp3 and GATA-3 on day 13. (C, D) Frequencies of GATA-3+ (C) and Foxp3+ (D) CD4+ cells (mean ± SD) in the peripheral blood of H. polygyrus-infected mice (left), I. ricinus-infested mice (middle), and H. polygyrus- and I. ricinus-coinfected mice (right) normalized to those in the peripheral blood of naive controls. Gray shading and vertical lines, period of larval tick feeding and the day of dissection, respectively. One-way ANOVAs with a Bonferroni-corrected pairwise t test were performed for every time point in the kinetic analysis. d, day. (E) Number of adult H. polygyrus worms isolated from small intestines on day 41. The box plot shows the medians and quartiles, with whiskers indicating 95% CIs. Differences were tested using an unpaired t test. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant. Data are for 5 or 6 mice per group.
Mentions: GraphPad Prism (version 5.01) software (San Diego, CA, USA) was used for the plotting and statistical analysis of the experimental infection data. The data were tested for statistically significant differences using an unpaired t test, one-way analysis of variance (ANOVA) with a Bonferroni-corrected posttest (see Fig. 3 and 5), and two-way-ANOVA (see Fig. 2) under the assumption of a normal distribution of the FACS fluorescence data, ELISA optical density data, and the majority of the experimental parasite infection data. The posttests following the two-way ANOVA for individual pairs using the Bonferroni correction were performed with the posttest calculator (GraphPad Software). The number of engorged tick nymphs and the molting rate in Fig. 7A and D, respectively, and the cell counts in Fig. S1B in the supplemental material were not normally distributed, and differences were tested using the Mann-Whitney U test. Differences with P values below 0.05 were considered to be significant.

Bottom Line: In a parasitological survey of wild mice in Berlin, Germany, approximately 40% of Ixodes ricinus-infested animals simultaneously harbored a nematode of the genus Heligmosomoides We therefore aimed to analyze the immunological impact of the nematode/tick coinfection as well as its effect on the tick-borne pathogen Borrelia afzelii Hosts experimentally coinfected with Heligmosomoides polygyrus and larval/nymphal I. ricinus ticks developed substantially stronger systemic type 2 T helper cell (Th2) responses, on the basis of the levels of GATA-3 and interleukin-13 expression, than mice infected with a single pathogen.During repeated larval infestations, however, anti-tick Th2 reactivity and an observed partial immunity to tick feeding were unaffected by concurrent nematode infections.Importantly, the strong systemic Th2 immune response in coinfected mice did not affect susceptibility to tick-borne B. afzelii An observed trend for decreased local and systemic Th1 reactivity against B. afzelii in coinfected mice did not result in a higher spirochete burden, nor did it facilitate bacterial dissemination or induce signs of immunopathology.

View Article: PubMed Central - PubMed

Affiliation: Institute of Immunology, Centre of Infection Medicine, Freie Universität Berlin, Berlin, Germany Institute of Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.

No MeSH data available.


Related in: MedlinePlus