Type 2 Innate Immunity in Helminth Infection Is Induced Redundantly and Acts Autonomously following CD11c<sup>+</sup>Cell Depletion

Smith, Katherine A.; Harcus, Yvonne; Garbi, Natalio; Hämmerling, Günter J.; MacDonald, Andrew S.; Maizels, Rick M.

doi:10.1128/iai.00436-12

Cited by 53 publications

(58 citation statements)

References 69 publications

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“…This has been shown in mice were knock-out individuals depleted of transcriptional factors IRF3 and IRF7 were still able to mount a chemokine mediated antiviral immune response [28]. Similar findings have been shown in a response to parasitic helminths, were innate immunity can be induced via alternative pathways [29]. In our data, we could clearly distinguish between genes generally expressed in response to trematode infection and those only activated against specific clones.…”

Section: Discussionsupporting

confidence: 86%

Specific Gene Expression Responses to Parasite Genotypes Reveal Redundancy of Innate Immunity in Vertebrates

et al. 2014

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Vertebrate innate immunity is the first line of defense against an invading pathogen and has long been assumed to be largely unspecific with respect to parasite/pathogen species. However, recent phenotypic evidence suggests that immunogenetic variation, i.e. allelic variability in genes associated with the immune system, results in host-parasite genotype-by-genotype interactions and thus specific innate immune responses. Immunogenetic variation is common in all vertebrate taxa and this reflects an effective immunological function in complex environments. However, the underlying variability in host gene expression patterns as response of innate immunity to within-species genetic diversity of macroparasites in vertebrates is unknown. We hypothesized that intra-specific variation among parasite genotypes must be reflected in host gene expression patterns. Here we used high-throughput RNA-sequencing to examine the effect of parasite genotypes on gene expression patterns of a vertebrate host, the three-spined stickleback (Gasterosteus aculeatus). By infecting naïve fish with distinct trematode genotypes of the species Diplostomum pseudospathaceum we show that gene activity of innate immunity in three-spined sticklebacks depended on the identity of an infecting macroparasite genotype. In addition to a suite of genes indicative for a general response against the trematode we also find parasite-strain specific gene expression, in particular in the complement system genes, despite similar infection rates of single clone treatments. The observed discrepancy between infection rates and gene expression indicates the presence of alternative pathways which execute similar functions. This suggests that the innate immune system can induce redundant responses specific to parasite genotypes.

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Section: Discussionsupporting

confidence: 86%

Specific Gene Expression Responses to Parasite Genotypes Reveal Redundancy of Innate Immunity in Vertebrates

et al. 2014

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“…The cell numbers were analyzed in the BALF and lungs at 6 dpi with a lethal dose of A/PR8/34 virus. The markers for flow cytometry were used to separate populations, such as neutrophils and monocytes (28,29). Importantly, we observed that the numbers of monocytes (CD11b ϩ Ly6c hi F4/ 80 ϩ ) in the BALF and lungs of immune WT mice were lower than those in nonimmune WT and CD47KO mice, but they were higher than those in immune CD47KO mice (Fig.…”

Section: Cd47ko Mice Induce Increased Virus-specific Igg Antibodies Amentioning

confidence: 81%

CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination against Influenza Virus

Lee

et al. 2016

J Virol

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An integrin-associated protein CD47, which is a ligand for the inhibitory receptor signal regulatory protein ␣, is expressed on B and T cells, as well as on most innate immune cells. However, the roles of CD47 in the immune responses to viral infection or vaccination remain unknown. We investigated the role of CD47 in inducing humoral immune responses after intranasal infection with virus or immunization with influenza virus-like particles (VLPs). Virus infection or vaccination with VLPs containing hemagglutinin from A/PR8/34 influenza virus induced higher levels of antigen-specific IgG2c isotype dominant antibodies in CD47-deficient (CD47KO) mice than in wild-type (WT) mice. CD47KO mice with vaccination showed greater protective efficacy against lethal challenge, as evidenced by no loss in body weight and reduced lung viral titers compared to WT mice. In addition, inflammatory responses which include cytokine production, leukocyte infiltrates, and gamma interferon-producing CD4 ؉ T cells, as well as an anti-inflammatory cytokine (interleukin-10), were reduced in the lungs of vaccinated CD47KO mice after challenge with influenza virus. Analysis of lymphocytes indicated that GL7 ؉ germinal center B cells were induced at higher levels in the draining lymph nodes of CD47KO mice compared to those in WT mice. Notably, CD47KO mice exhibited significant increases in the numbers of antigen-specific memory B cells in spleens and plasma cells in bone marrow despite their lower levels of background IgG antibodies. These results suggest that CD47 plays a role as a negative regulator in inducing protective immune responses to influenza vaccination. I nfluenza viruses are common pathogens in the respiratory tract that are highly contagious and can cause pulmonary diseases. Seasonal influenza virus variants annually cause significant levels of morbidity and mortality, mostly in infants, the elderly, and sick people (1, 2). Vaccination is the most effective measure to prevent infections with a variety of pathogens, including influenza virus. Virus-like particles (VLPs) are able to effectively stimulate antigen-presenting cells (APCs), which in turn activate T and B cells (3-6). It has been demonstrated that immunization with influenza VLPs can induce protective humoral responses against seasonal and pandemic influenza virus infections (7-9). However, the mechanisms for evoking long-lasting immune responses are largely unknown.CD47 is a transmembrane protein, which is first identified as integrin ␣v␤3. CD47 that is expressed on hematopoietic and nonhematopoietic cells can interact with an inhibitory receptor signal regulatory protein ␣ (SIRP␣) (10). SIRP␣ is also expressed on dendritic cells (DCs) and macrophages, whereas SIRP␣ is barely expressed on B and T cells (11,12). It has been demonstrated that CD47/CD47 and CD47/SIRP␣ interactions are important for DC and neutrophil migration (13,14). In addition, CD11b ϩ DCs in the lungs express both CD47 and SIRP␣, but CD103 ϩ DCs express only CD47. It was also demonstrated t...

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“…[14][15][16][17][18][19] The localization of specific DC subsets within the lymph node plays an important role for Th2 skewing against helminthic infection. In this regard, it has been demonstrated that after infection with helminths, antigen-bearing DCs upregulate the chemokine receptor CXCR5 and that CXCR5-expressing CD11c þ DCs migrate to the lymph node for Th2 skewing in H. polygyrus infection.…”

Section: Evidence For Th2 Polarization By Dcs Activated With Helminthmentioning

confidence: 99%

Molecular events by which dendritic cells promote Th2 immune protection in helmith infection

Méndez-Samperio¹

2016

Infectious Diseases

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Helminth parasites are a major cause of global infectious diseases, affecting nearly one quarter of the world's population. The common feature of helminth infections is to skew the immune system towards a T-helper 2 (Th2) response that helps to control disease. Dendritic cells (DCs), which are professional antigen-presenting cells, play a critical role for Th2 skewing against helminth parasites. However, the molecular mechanisms by which helminth antigens activate DCs for Th2 polarization have not yet been clearly defined. This review provides a focused update on the major role of DCs for inducing and/or enhancing Th2 immune responses in helminthic infection and will discuss the main signalling-dependent and independent mechanisms by which helminth antigens activate DCs for Th2 skewing.

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Type 2 Innate Immunity in Helminth Infection Is Induced Redundantly and Acts Autonomously following CD11c⁺Cell Depletion

Cited by 53 publications

References 69 publications

Specific Gene Expression Responses to Parasite Genotypes Reveal Redundancy of Innate Immunity in Vertebrates

Specific Gene Expression Responses to Parasite Genotypes Reveal Redundancy of Innate Immunity in Vertebrates

CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination against Influenza Virus

Molecular events by which dendritic cells promote Th2 immune protection in helmith infection

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Type 2 Innate Immunity in Helminth Infection Is Induced Redundantly and Acts Autonomously following CD11c+Cell Depletion

Cited by 53 publications

References 69 publications

Specific Gene Expression Responses to Parasite Genotypes Reveal Redundancy of Innate Immunity in Vertebrates

Specific Gene Expression Responses to Parasite Genotypes Reveal Redundancy of Innate Immunity in Vertebrates

CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination against Influenza Virus

Molecular events by which dendritic cells promote Th2 immune protection in helmith infection

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Type 2 Innate Immunity in Helminth Infection Is Induced Redundantly and Acts Autonomously following CD11c⁺Cell Depletion