Limits...
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

Systemic and local immune responses in mice coinfected with H. polygyrus and I. ricinus-transmitted B. afzelii (B. a.). (A) Experimental setup showing the time line (in days) of exposure to parasites and blood sampling. (B) Kinetics of GATA-3+ CD4+ cell frequencies (mean ± SD) in peripheral blood. Gray shading and the vertical line, period of nymphal tick feeding and the day of dissection, respectively. Asterisks indicate significant differences between the coinfected group and the group infested with I. ricinus only for every time point. (C to E) Production of IL-13 (C), IL-10 (D), and IFN-γ (E) by spleen and SLN CD4+ T cells stimulated with PMA-ionomycin and bulk cultures stimulated with B. afzelii antigen. Means and SDs are shown. Symbols represent the intracellular cytokine responses detected in cells from individual mice. Differences between groups were analyzed using unpaired t tests. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant. Data are for 6 mice per group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4862734&req=5

Figure 6: Systemic and local immune responses in mice coinfected with H. polygyrus and I. ricinus-transmitted B. afzelii (B. a.). (A) Experimental setup showing the time line (in days) of exposure to parasites and blood sampling. (B) Kinetics of GATA-3+ CD4+ cell frequencies (mean ± SD) in peripheral blood. Gray shading and the vertical line, period of nymphal tick feeding and the day of dissection, respectively. Asterisks indicate significant differences between the coinfected group and the group infested with I. ricinus only for every time point. (C to E) Production of IL-13 (C), IL-10 (D), and IFN-γ (E) by spleen and SLN CD4+ T cells stimulated with PMA-ionomycin and bulk cultures stimulated with B. afzelii antigen. Means and SDs are shown. Symbols represent the intracellular cytokine responses detected in cells from individual mice. Differences between groups were analyzed using unpaired t tests. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant. Data are for 6 mice per group.

Mentions: Next, we examined whether increased systemic Th2 responses in mice coinfected with ticks and intestinal nematodes might inhibit Th1 responses against tick-borne spirochetes. Borrelia afzelii-infected I. ricinus nymphs were permitted to feed on mice infected with H. polygyrus and naive controls. As the maximum systemic Th2 response, based on peripheral blood Th2 cell frequencies, occurred in the second week of H. polygyrus infections (Fig. 3C), we chose day 16 after nematode infection for tick attachment (Fig. 6A). High frequencies of GATA-3+ Th2 cells in the peripheral blood briefly before and during tick feeding were confirmed (Fig. 6B). Mice were dissected 19 days after I. ricinus infestation, when B. afzelii dissemination in the natural rodent hosts results in maximum infectivity for feeding tick larvae (3). Upon PMA-ionomycin-induced stimulation, spleen cells from mice coinfected with nematodes and ticks again responded with the highest frequencies of CD4+ cells producing IL-13, IL-10, and IFN-γ (Fig. 6C to E). A similar response to PMA-ionomycin-induced stimulation was observed for local CD4+ T cells derived from SLNs (Fig. 6C to E). To survey antispirochete responses, bulk cultures were stimulated with B. afzelii antigen. Surprisingly, low levels of spirochete-specific IL-13 production by splenocytes but not by SLN cells were detectable in both groups of mice infested with B. afzelii-infected ticks (Fig. 6C). Splenocytes from mice infested only with Borrelia-infected ticks produced high levels of IL-10 in response to spirochete antigen, but this response was significantly suppressed in spleen cells derived from mice coinfected with nematodes and ticks. In contrast, spirochete-specific IL-10 production by local SLN cells was unaffected by the presence of intestinal nematodes (Fig. 6D). Although the highest frequencies of CD4+ IFN-γ+ cells were detected in the spleens and SLNs of coinfected mice, the B. afzelii antigen-specific responses of splenocytes and SLN cells appeared to be slightly but not significantly lower in mice coinfected with nematodes and ticks, which was also reflected by anti-CD3/anti-CD28 antibody stimulation (Fig. 6D and not shown). Thus, systemic and local Borrelia-specific Th1 reactivity is only mildly affected, if it is affected at all, by a concurrent intestinal nematode infection.


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)

Systemic and local immune responses in mice coinfected with H. polygyrus and I. ricinus-transmitted B. afzelii (B. a.). (A) Experimental setup showing the time line (in days) of exposure to parasites and blood sampling. (B) Kinetics of GATA-3+ CD4+ cell frequencies (mean ± SD) in peripheral blood. Gray shading and the vertical line, period of nymphal tick feeding and the day of dissection, respectively. Asterisks indicate significant differences between the coinfected group and the group infested with I. ricinus only for every time point. (C to E) Production of IL-13 (C), IL-10 (D), and IFN-γ (E) by spleen and SLN CD4+ T cells stimulated with PMA-ionomycin and bulk cultures stimulated with B. afzelii antigen. Means and SDs are shown. Symbols represent the intracellular cytokine responses detected in cells from individual mice. Differences between groups were analyzed using unpaired t tests. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant. Data are for 6 mice per group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Systemic and local immune responses in mice coinfected with H. polygyrus and I. ricinus-transmitted B. afzelii (B. a.). (A) Experimental setup showing the time line (in days) of exposure to parasites and blood sampling. (B) Kinetics of GATA-3+ CD4+ cell frequencies (mean ± SD) in peripheral blood. Gray shading and the vertical line, period of nymphal tick feeding and the day of dissection, respectively. Asterisks indicate significant differences between the coinfected group and the group infested with I. ricinus only for every time point. (C to E) Production of IL-13 (C), IL-10 (D), and IFN-γ (E) by spleen and SLN CD4+ T cells stimulated with PMA-ionomycin and bulk cultures stimulated with B. afzelii antigen. Means and SDs are shown. Symbols represent the intracellular cytokine responses detected in cells from individual mice. Differences between groups were analyzed using unpaired t tests. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant. Data are for 6 mice per group.
Mentions: Next, we examined whether increased systemic Th2 responses in mice coinfected with ticks and intestinal nematodes might inhibit Th1 responses against tick-borne spirochetes. Borrelia afzelii-infected I. ricinus nymphs were permitted to feed on mice infected with H. polygyrus and naive controls. As the maximum systemic Th2 response, based on peripheral blood Th2 cell frequencies, occurred in the second week of H. polygyrus infections (Fig. 3C), we chose day 16 after nematode infection for tick attachment (Fig. 6A). High frequencies of GATA-3+ Th2 cells in the peripheral blood briefly before and during tick feeding were confirmed (Fig. 6B). Mice were dissected 19 days after I. ricinus infestation, when B. afzelii dissemination in the natural rodent hosts results in maximum infectivity for feeding tick larvae (3). Upon PMA-ionomycin-induced stimulation, spleen cells from mice coinfected with nematodes and ticks again responded with the highest frequencies of CD4+ cells producing IL-13, IL-10, and IFN-γ (Fig. 6C to E). A similar response to PMA-ionomycin-induced stimulation was observed for local CD4+ T cells derived from SLNs (Fig. 6C to E). To survey antispirochete responses, bulk cultures were stimulated with B. afzelii antigen. Surprisingly, low levels of spirochete-specific IL-13 production by splenocytes but not by SLN cells were detectable in both groups of mice infested with B. afzelii-infected ticks (Fig. 6C). Splenocytes from mice infested only with Borrelia-infected ticks produced high levels of IL-10 in response to spirochete antigen, but this response was significantly suppressed in spleen cells derived from mice coinfected with nematodes and ticks. In contrast, spirochete-specific IL-10 production by local SLN cells was unaffected by the presence of intestinal nematodes (Fig. 6D). Although the highest frequencies of CD4+ IFN-γ+ cells were detected in the spleens and SLNs of coinfected mice, the B. afzelii antigen-specific responses of splenocytes and SLN cells appeared to be slightly but not significantly lower in mice coinfected with nematodes and ticks, which was also reflected by anti-CD3/anti-CD28 antibody stimulation (Fig. 6D and not shown). Thus, systemic and local Borrelia-specific Th1 reactivity is only mildly affected, if it is affected at all, by a concurrent intestinal nematode infection.

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