Cutting Edge: Helminth Coinfection Blocks Effector Differentiation of CD8 T Cells through Alternate Host Th2- and IL-10–Mediated Responses

Marple, Andrew; Wu, Wenhui; Shah, Suhagi; Zhao, Yanlin; Du, Peicheng; Gause, William C.; Yap, George

doi:10.4049/jimmunol.1601741

Cited by 25 publications

(21 citation statements)

References 22 publications

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“…Indeed, helminth infections can down-modulate allergy or inflammatory bowel disease through various mechanisms 38 , but have also been involved in modulating the ability of the infected host to control virus infections. Several groups have shown using C57BL/6 mice that exposure to H. polygyrus or S. mansoni eggs enhanced reactivation from latency of MuHV-4 through changes in the IL-4/IFN-γ balance 10 and also that intestine dwelling helminths could alter effector CD8 + T cell responses against a subsequent viral 8 or protozoal infection 39 . Nevertheless, these studies did not investigate how helminths could affect bystander memory T cells such as the T VM compartment.…”

Section: Discussionmentioning

confidence: 99%

Helminth-induced IL-4 expands bystander memory CD8+ T cells for early control of viral infection

et al. 2018

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Infection with parasitic helminths can imprint the immune system to modulate bystander inflammatory processes. Bystander or virtual memory CD8+ T cells (TVM) are non-conventional T cells displaying memory properties that can be generated through responsiveness to interleukin (IL)-4. However, it is not clear if helminth-induced type 2 immunity functionally affects the TVM compartment. Here, we show that helminths expand CD44hiCD62LhiCXCR3hiCD49dlo TVM cells through direct IL-4 signaling in CD8+ T cells. Importantly, helminth-mediated conditioning of TVM cells provided enhanced control of acute respiratory infection with the murid gammaherpesvirus 4 (MuHV-4). This enhanced control of MuHV-4 infection could further be explained by an increase in antigen-specific CD8+ T cell effector responses in the lung and was directly dependent on IL-4 signaling. These results demonstrate that IL-4 during helminth infection can non-specifically condition CD8+ T cells, leading to a subsequently raised antigen-specific CD8+ T cell activation that enhances control of viral infection.

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Section: Discussionmentioning

confidence: 99%

Helminth-induced IL-4 expands bystander memory CD8+ T cells for early control of viral infection

et al. 2018

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“…On the other hand, CD8 + T lymphocytes from patients with schistosomiasis presented a higher frequency of CTLA-4 than patients with leishmaniasis. In coinfections by the helminth Heligmosomoides polygyrus and the protozoan Toxoplasma gondii , the nematode-induced response sup-presses CD8 + T lymphocytes with decreased IFN-γ (Marple et al, 2017). …”

Section: Discussionmentioning

confidence: 99%

Susceptibility of dendritic cells from individuals with schistosomiasis to infection by Leishmania braziliensis

Lopes

Almeida

Souza

et al. 2018

Molecular Immunology

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Coinfection with leishmaniasis and schistosomiasis has been associated with increased time to healing of cutaneous lesions of leishmaniasis. The objective of this study was to evaluate the effect of Leishmania braziliensis infection on co-cultures of monocyte-derived dendritic cells (MoDCs) with autologous lymphocytes from patients with schistosomiasis and patients with cutaneous leishmaniasis. MoDCs were differentiated from peripheral blood monocytes, isolated by magnetic beads, infected with L. braziliensis, and co-cultured with autologous lymphocytes. Expression of HLA-DR, CD1a, CD83, CD80, CD86, CD40, and the IL-10 receptor (IL-10R) on MoDCs as well as CD28, CD40L, CD25, and CTLA-4 on lymphocytes were evaluated by flow cytometry. The production of the cytokines IL-10, TNF, IL-12p40, and IFN-γ were evaluated by sandwich ELISA of the culture supernatant. The infectivity evaluation was performed by light microscopy after concentration of cells by cytospin and Giemsa staining. It was observed that the frequency of MoDCs expressing CD83, CD80, and CD86 as well as the MFI of HLA-DR were smaller in the group of patients with schistosomiasis compared to the group of patients with leishmaniasis. On the other hand, the frequency of IL-10R on MoDCs was higher in patients with schistosomiasis than in patients with leishmaniasis. CD4+ and CD8+ T lymphocytes from patients with schis-tosomiasis presented a lower frequency of CD28 and a higher frequency of CTLA-4 compared to lymphocytes from patients with leishmaniasis. Levels of IL-10 were higher in the supernatants of co-cultures from individuals with schistosomiasis compared to those with leishmaniasis. However, levels of TNF, IL-12p40, and IFN-γ were lower in the group of individuals with schistosomiasis. Regarding the frequency of MoDCs infected by L. braziliensis after 72 h in culture, it was observed that higher frequencies of cells from patients with schistosomiasis were infected compared to cells from patients with leishmaniasis. It was concluded that MoDCs from patients with schistosomiasis are more likely to be infected by L. braziliensis, possibly due to a lower degree of activation and a regulatory profile.

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“…Co-infection with T. gondii in these mice was instead accompanied by a shift toward a non-protective helminth-specific Th1 response ( 44 ). Conversely, separate studies have shown that H. polygyrus co-infection can negatively impact upon CD8 + T cell differentiation and cytokine production in response to T. gondii infection ( 45 , 46 ). Conventional dendritic cells from the H. polygyrus co-infected mice also had reduced expression of IL-12 ( 46 ).…”

Section: Apicomplexan Parasitesmentioning

confidence: 99%

The Influence of Parasite Infections on Host Immunity to Co-infection With Other Pathogens

Mabbott

2018

Front. Immunol.

122

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Parasites have evolved a wide range of mechanisms that they use to evade or manipulate the host's immune response and establish infection. The majority of the in vivo studies that have investigated these host-parasite interactions have been undertaken in experimental animals, especially rodents, which were housed and maintained to a high microbiological status. However, in the field situation it is increasingly apparent that pathogen co-infections within the same host are a common occurrence. For example, chronic infection with pathogens including malarial parasites, soil-transmitted helminths, Mycobacterium tuberculosis and viruses such as HIV may affect a third of the human population of some developing countries. Increasing evidence shows that co-infection with these pathogens may alter susceptibility to other important pathogens, and/or influence vaccine efficacy through their effects on host immune responsiveness. Co-infection with certain pathogens may also hinder accurate disease diagnosis. This review summarizes our current understanding of how the host's immune response to infection with different types of parasites can influence susceptibility to infection with other pathogenic microorganisms. A greater understanding of how infectious disease susceptibility and pathogenesis can be influenced by parasite co-infections will enhance disease diagnosis and the design of novel vaccines or therapeutics to more effectively control the spread of infectious diseases.

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Cutting Edge: Helminth Coinfection Blocks Effector Differentiation of CD8 T Cells through Alternate Host Th2- and IL-10–Mediated Responses

Cited by 25 publications

References 22 publications

Helminth-induced IL-4 expands bystander memory CD8+ T cells for early control of viral infection

Helminth-induced IL-4 expands bystander memory CD8+ T cells for early control of viral infection

Susceptibility of dendritic cells from individuals with schistosomiasis to infection by Leishmania braziliensis

The Influence of Parasite Infections on Host Immunity to Co-infection With Other Pathogens

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