Host Defense Versus Immunosuppression: Unisexual Infection With Male or Female Schistosoma mansoni Differentially Impacts the Immune Response Against Invading Cercariae

Sombetzki, Martina; Koslowski, Nicole; Rabes, Anne; Seneberg, Sonja; Winkelmann, Franziska; Fritzsche, Carlos; Loebermann, Micha; Reisinger, Emil C.

doi:10.3389/fimmu.2018.00861

Cited by 21 publications

(26 citation statements)

References 38 publications

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“…While we have focused on male-only infections, a recent study reported that infection of mice with female-only adult worms (FO) resulted in reduced proinflammatory cytokine production compared to that with male-only adult worm (MO) infections (24). Further investigation is required on S. mansoni female-only adult worm infection modulation of the microbiome and intestinal inflammation.…”

Section: Discussionmentioning

confidence: 99%

Schistosoma mansoni Worm Infection Regulates the Intestinal Microbiota and Susceptibility to Colitis

et al. 2019

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Infection with parasite helminths induces potent modulation of the immune system of the host. Epidemiological and animal studies have shown that helminth infections can suppress or exacerbate unrelated autoimmune, allergic, and other inflammatory disorders. There is growing evidence that helminth infectionmediated suppression of bystander inflammatory responses is influenced by alterations in the intestinal microbiome modulating metabolic and immune functions of the infected host. We analyzed the fecal microbiota of mice infected with adult male Schistosoma mansoni worms, which are less susceptible to experimental colitis, and male-and female-worm-infected mice, which are highly sensitive to colitis. While both groups of infected mice developed a disrupted microbiota, there were marked alterations in mice with male and female worm infections. Antibiotic-treated recipients that were cohoused with both types of S. mansoni worm-infected mice acquired a colitogenic microbiome, leading to increased susceptibility to experimental colitis. Following anthelmintic treatment to remove worms from worm-only-infected mice, the mice developed exacerbated colitis. This study provides evidence that adult male S. mansoni worm infection modulates the host's immune system and suppresses bystander colitis while limiting dysbiosis of the host's intestinal microbiome during infection.

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Section: Discussionmentioning

confidence: 99%

Schistosoma mansoni Worm Infection Regulates the Intestinal Microbiota and Susceptibility to Colitis

et al. 2019

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“…rTrCB2 activated BMDCs much more effectively than cercarial homogenate, and apart from Il12a and Ccl5, it also induced expression of Cxcl10 , Il10 and Il33 . CCL5 (RANTES) and CXCL10 (IP‐10) were observed in the skin after S. mansoni infection 38 as well and could induce production of IL‐6 39 which was present in the skin early after T. regenti infection 16 or promote Th1 response, 40‐42 respectively. Furthermore, CXCL10 regulates the proportion of CD4+T‐bet+ cells in the circulation and lymph nodes during the infection 43 .…”

Section: Discussionmentioning

confidence: 99%

The peripheral immune response of mice infected with a neuropathogenic schistosome

Majer

Macháček

Súkeníková

et al. 2020

Parasite Immunology

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Helminths do often invade the central nervous system (CNS) of vertebrates, including humans, causing severe pathologies, such as in the case of neurocysticercosis (NCC) or neurotoxocarosis. 1 Although the CNS was formerly considered an immune-privileged site with a limited capacity to develop an adaptive immune response, this view has recently been revisited. 2,3 Inflammatory cells are recruited into the infected CNS as well as pathogen-specific T cells, which were primed in the periphery. 4 The polarization of helminth-specific T helper (Th) cells largely orchestrates the host immune response. Th1 and Th17 populations are usually associated with host pathology, contrary to Th2 response and expansion of regulatory T cells (Treg) which suggest asymptomatic or mild infection. 5 For example, symptomatic NCC is linked to increased serum levels of proinflammatory cytokines 6 while Th2/ Treg milieu is related to asymptomatic NCC. 6-9 However, it is not very clear how the host immune response is influenced by the cysts present directly in the CNS and those disseminated in other body parts. The same applies to Toxocara spp. which exhibits a marked Abstract Trichobilharzia regenti (Schistosomatidae) percutaneously infects birds and mammals and invades their central nervous system (CNS). Here, we characterized the peripheral immune response of infected mice and showed how it was influenced by the parasite-induced inflammation in the skin and the CNS. As revealed by flow cytometry, T cells expanded in the spleen and the CNS-draining lymph nodes 7-14 days post-infection. Both T-bet+ and GATA-3+ T cells were markedly elevated suggesting a mixed type 1/2 immune response. However, it dropped after 7 dpi most likely being unaffected by the neuroinflammation. Splenocytes from infected mice produced a high amount of IFN-γ and, to a lesser extent, IL-10, IL-4 and IL-17 after in vitro stimulation by cercarial homogenate. Nevertheless, it had only a limited capacity to alter the maturation status of bone marrow-derived dendritic cells (BMDCs), contrary to the recombinant T. regenti cathepsin B2, which also strongly augmented expression of Ccl5, Cxcl10, Il12a, Il33 and Il10 by BMDCs. Taken together, mice infected with T. regenti developed the mixed type 1/2 immune response, which was driven by the early skin inflammation rather than the late neuroinflammation. Parasite peptidases might play an active role in triggering the host immune response. K E Y W O R D S cathepsin B, central nervous system, dendritic cells, lymph nodes, skin, spleen, T lymphocytes

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“…The availability of controlled human infection model for schistosome infection may revolutionize the development of schistosomiasis vaccines in the future. In addition, a growing number of studies have been performed to investigate the influence of unisexual schistosome infection on the host's immune system and intestinal microbiota, which provide a promising prospect for new immune modulatory therapies [40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Duplex real-time PCR for sexing Schistosoma japonicum cercariae based on W chromosome-specific genes and its applications

et al. 2020

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As a unique feature among otherwise hermaphroditic trematodes, Schistosoma species are gonochoric parasites whose sex is genetically determined (ZZ for males and ZW for females). However, schistosome larvae are morphologically identical, and sex can only be discriminated by molecular methods. Here, we integrated published Schistosoma. japonicum transcriptome and genome data to identify W chromosome-specific genes as sex biomarkers. Three W chromosome-specific genes of S. japonicum were identified as sex biomarkers from a panel of 12 genes expressed only in females. An efficient duplex realtime PCR (qPCR) method for sexing cercariae was developed which could identify the sex of cercariae within 2 h without DNA extraction. Moreover, this method can be used to identify not only single-sex but also mixed-sex schistosome-infected snails. We observed a nearly equal proportion of single-male, single-female, and mixed-sex schistosome infections in artificially infected snails. Sex-known schistosome-infected snail models can be efficiently constructed with the aid of duplex qPCR. A field study revealed that single-sex schistosome infections were predominant among naturally infected snails. Finally, a schistosomiasis mouse model based on sex-known cercariae infection was shown to be more reliable than a model based on sex-unknown cercariae infection. The developed duplex qPCR method for sexing S. japonicum cercariae can be widely used for schistosomiasis modeling, genetic experiments, and field-based molecular epidemiological studies.

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Host Defense Versus Immunosuppression: Unisexual Infection With Male or Female Schistosoma mansoni Differentially Impacts the Immune Response Against Invading Cercariae

Cited by 21 publications

References 38 publications

Schistosoma mansoni Worm Infection Regulates the Intestinal Microbiota and Susceptibility to Colitis

Schistosoma mansoni Worm Infection Regulates the Intestinal Microbiota and Susceptibility to Colitis

The peripheral immune response of mice infected with a neuropathogenic schistosome

Duplex real-time PCR for sexing Schistosoma japonicum cercariae based on W chromosome-specific genes and its applications

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