IL-4 and IFN-γ induced by human immunodeficiency virus vaccine in a schistosome infection model

Yin, Jiangmei; Dai, Anlan; Arango, Tatiana; Kasinathan, Ravi S.; Greenberg, Robert M.; Boyer, Jean

doi:10.4161/hv.22142

Cited by 2 publications

(3 citation statements)

References 39 publications

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“…As we expected, our data confirmed that prior to vaccination, Sm-infected mice elicited predominantly Th2 responses and a decreased Th1 cytokine profile ( Fig 1A and 1B ; S1 Fig ), had impaired Th1 cytokine-producing CD8+ and CD4+ T cells ( Fig 1C ) and an increase in Th2 total antibodies in serum ( Fig 1D ) as well as enlarged spleens and livers ( Fig 5C and 5D ) compared to uninfected mice. These findings are consistent with previous reports that demonstrate that Sm infection and a host of other helminths skews the host’s immune responses from a Th1 towards a Th2 type with egg deposition and increased production of IL-4 as key driving forces [ 23 , 26 , 27 , 63 , 68 – 72 ]. Our data also agrees with previous studies that have demonstrated that IL-10 is also responsible for down-regulation of Th1 responses that is observed in schistosome infections [ 73 , 74 ].…”

Section: Discussionsupporting

confidence: 93%

“…During chronic schistosomiasis, parasite eggs are lodged in the liver and intestinal tissue [ 21 , 22 ] resulting in predominantly T-helper 2 (Th2) immune responses [ 23 – 27 ] and the induction of anti-inflammatory regulatory T-cells (Treg) which suppress the innate and adaptive T- and B-cell responses [ 24 , 28 , 29 ]. This has been shown to lead to general hyporesponsiveness which may adversely impact standard immunizations, by suppressing immune responses to Th1-type vaccine and impairing the expansion of pathogen-specific cytotoxic T lymphocyte (CTL) responses [ 30 – 37 ].…”

Section: Introductionmentioning

confidence: 99%

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Chronic schistosomiasis suppresses HIV-specific responses to DNA-MVA and MVA-gp140 Env vaccine regimens despite antihelminthic treatment and increases helminth-associated pathology in a mouse model

et al. 2018

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Future HIV vaccines are expected to induce effective Th1 cell-mediated and Env-specific antibody responses that are necessary to offer protective immunity to HIV infection. However, HIV infections are highly prevalent in helminth endemic areas. Helminth infections induce polarised Th2 responses that may impair HIV vaccine-generated Th1 responses. In this study, we tested if Schistosoma mansoni (Sm) infection altered immune responses to SAAVI candidate HIV vaccines (DNA and MVA) and an HIV-1 gp140 Env protein vaccine (gp140) and whether parasite elimination by chemotherapy or the presence of Sm eggs (SmE) in the absence of active infection influenced the immunogenicity of these vaccines. In addition, we evaluated helminth-associated pathology in DNA and MVA vaccination groups. Mice were chronically infected with Sm and vaccinated with DNA+MVA in a prime+boost combination or MVA+gp140 in concurrent combination regimens. Some Sm-infected mice were treated with praziquantel (PZQ) prior to vaccinations. Other mice were inoculated with SmE before receiving vaccinations. Unvaccinated mice without Sm infection or SmE inoculation served as controls. HIV responses were evaluated in the blood and spleen while Sm-associated pathology was evaluated in the livers. Sm-infected mice had significantly lower magnitudes of HIV-specific cellular responses after vaccination with DNA+MVA or MVA+gp140 compared to uninfected control mice. Similarly, gp140 Env-specific antibody responses were significantly lower in vaccinated Sm-infected mice compared to controls. Treatment with PZQ partially restored cellular but not humoral immune responses in vaccinated Sm-infected mice. Gp140 Env-specific antibody responses were attenuated in mice that were inoculated with SmE compared to controls. Lastly, Sm-infected mice that were vaccinated with DNA+MVA displayed exacerbated liver pathology as indicated by larger granulomas and increased hepatosplenomegaly when compared with unvaccinated Sm-infected mice. This study shows that chronic schistosomiasis attenuates both HIV-specific T-cell and antibody responses and parasite elimination by chemotherapy may partially restore cellular but not antibody immunity, with additional data suggesting that the presence of SmE retained in the tissues after antihelminthic therapy contributes to lack of full immune restoration. Our data further suggest that helminthiasis may compromise HIV vaccine safety. Overall, these findings suggested a potential negative impact on future HIV vaccinations by helminthiasis in endemic areas.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Chronic schistosomiasis suppresses HIV-specific responses to DNA-MVA and MVA-gp140 Env vaccine regimens despite antihelminthic treatment and increases helminth-associated pathology in a mouse model

et al. 2018

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“…Schistosoma ) [23] , [24] , [25] . The co-infection of Human immunodeficiency virus (HIV) and helminth parasites, such as Schistosoma spp, is dramatically frequent in sub-Saharan Africa and it adversely impacts the ability of the immune system to control HIV progression [26] , [27] . It has been shown that IL-4, a prototype Th2 cytokine, increases Simian immunodeficiency virus load in infected rhesus macaques, despite enhanced antibody responses [26] .…”

Section: Introductionmentioning

confidence: 99%

IL-4 Suppresses the Responses to TLR7 and TLR9 Stimulation and Increases the Permissiveness to Retroviral Infection of Murine Conventional Dendritic Cells

Sriram

Chain

et al. 2014

PLoS ONE

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Th2-inducing pathological conditions such as parasitic diseases increase susceptibility to viral infections through yet unclear mechanisms. We have previously reported that IL-4, a pivotal Th2 cytokine, suppresses the response of murine bone-marrow-derived conventional dendritic cells (cDCs) and splenic DCs to Type I interferons (IFNs). Here, we analyzed cDC responses to TLR7 and TLR9 ligands, R848 and CpGs, respectively. We found that IL-4 suppressed the gene expression of IFNβ and IFN-responsive genes (IRGs) upon TLR7 and TLR9 stimulation. IL-4 also inhibited IFN-dependent MHC Class I expression and amplification of IFN signaling pathways triggered upon TLR stimulation, as indicated by the suppression of IRF7 and STAT2. Moreover, IL-4 suppressed TLR7- and TLR9-induced cDC production of pro-inflammatory cytokines such as TNFα, IL-12p70 and IL-6 by inhibiting IFN-dependent and NFκB-dependent responses. IL-4 similarly suppressed TLR responses in splenic DCs. IL-4 inhibition of IRGs and pro-inflammatory cytokine production upon TLR7 and TLR9 stimulation was STAT6-dependent, since DCs from STAT6-KO mice were resistant to the IL-4 suppression. Analysis of SOCS molecules (SOCS1, −2 and −3) showed that IL-4 induces SOCS1 and SOCS2 in a STAT6 dependent manner and suggest that IL-4 suppression could be mediated by SOCS molecules, in particular SOCS2. IL-4 also decreased the IFN response and increased permissiveness to viral infection of cDCs exposed to a HIV-based lentivirus. Our results indicate that IL-4 modulates and counteracts pro-inflammatory stimulation induced by TLR7 and TLR9 and it may negatively affect responses against viruses and intracellular parasites.

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IL-4 and IFN-γ induced by human immunodeficiency virus vaccine in a schistosome infection model

Cited by 2 publications

References 39 publications

Chronic schistosomiasis suppresses HIV-specific responses to DNA-MVA and MVA-gp140 Env vaccine regimens despite antihelminthic treatment and increases helminth-associated pathology in a mouse model

Chronic schistosomiasis suppresses HIV-specific responses to DNA-MVA and MVA-gp140 Env vaccine regimens despite antihelminthic treatment and increases helminth-associated pathology in a mouse model

IL-4 Suppresses the Responses to TLR7 and TLR9 Stimulation and Increases the Permissiveness to Retroviral Infection of Murine Conventional Dendritic Cells

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