scholarly journals A Comparative Study of the Innate Humoral Immune Response to Avian Influenza Virus in Wild and Domestic Mallards

2020 ◽  
Vol 11 ◽  
Author(s):  
Jacintha G. B. van Dijk ◽  
Josanne H. Verhagen ◽  
Arne Hegemann ◽  
Conny Tolf ◽  
Jenny Olofsson ◽  
...  
Keyword(s):  
Immune Response ◽  
Avian Influenza ◽  
Immune Function ◽  
Innate Immune Response ◽  
Acute Phase ◽  
Humoral Immune Response ◽  
Innate Immune ◽  
Wild Type ◽  
Free Living ◽  
Humoral Immune

Domestic mallards (Anas platyrhynchos domesticus) are traditionally used as a model to investigate infection dynamics and immune responses to low pathogenic avian influenza viruses (LPAIVs) in free-living mallards. However, it is unclear whether the immune response of domestic birds reflects the response of their free-living counterparts naturally exposed to these viruses. We investigated the extent to which the innate humoral immune response was similar among (i) wild-type domestic mallards in primary and secondary infection with LPAIV H4N6 in a laboratory setting (laboratory mallards), (ii) wild-type domestic mallards naturally exposed to LPAIVs in a semi-natural setting (sentinel mallards), and (iii) free-living mallards naturally exposed to LPAIVs. We quantified innate humoral immune function by measuring non-specific natural antibodies (agglutination), complement activity (lysis), and the acute phase protein haptoglobin. We demonstrate that complement activity in the first 3 days after LPAIV exposure was higher in primary-exposed laboratory mallards than in sentinel and free-living mallards. LPAIV H4N6 likely activated the complement system and the acute phase response in primary-exposed laboratory mallards, as lysis was higher and haptoglobin lower at day 3 and 7 post-exposure compared to baseline immune function measured prior to exposure. There were no differences observed in natural antibody and haptoglobin concentrations among laboratory, sentinel, and free-living mallards in the first 3 days after LPAIV exposure. Our study demonstrates that, based on the three innate humoral immune parameters measured, domestic mallards seem an appropriate model to investigate innate immunology of their free-living counterparts, albeit the innate immune response of secondary-LPAIV exposed mallards is a better proxy for the innate immune response in pre-exposed free-living mallards than that of immunologically naïve mallards.

TLR4 regulates rabies virus-induced humoral immunity through recruitment of cDC2 to lymph organs

2021 ◽  
Author(s):  
Chen Chen ◽  
Chengguang Zhang ◽  
Haoqi Li ◽  
Zongmei Wang ◽  
Yueming Yuan ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Rabies Virus ◽  
Humoral Immunity ◽  
Humoral Immune Response ◽  
Critical Role ◽  
Wild Type ◽  
Humoral Immune ◽  
Specific Igg ◽  
Molecular Patterns

Rabies, caused by rabies virus (RABV), is fatal to both humans and animals around the world. Effective clinical therapy for rabies has not been achieved, and vaccination is the most effective means of preventing and controlling rabies. Although different vaccines, such as live attenuated and inactivated vaccines, can induce different immune responses, different expression of pattern recognition receptors (PRRs) also causes diverse immune responses. Toll-like receptor 4 (TLR4) is a pivotal PRR that induces cytokine production and bridges innate and adaptive immunity. Importantly, TLR4 recognizes various virus-derived pathogen-associated molecular patterns (PAMPs) and virus-induced damage-associated molecular patterns (DAMPs), usually leading to the activation of immune cells. However, the role of TLR4 in the humoral immune response induced by RABV has not been revealed yet. Based on TLR4-deficient ( TLR4 -/- ) and wild-type (WT) mouse models, we report that TLR4-dependent recruitment of the conventional type-2 dendritic cells (CD8α - CD11b + cDC2) into secondary lymph organs (SLOs) is critical for antigen presentation. cDC2-initiated differentiation of Tfh cells promotes the proliferation of germinal centre (GC) B cells, the formation of GCs, and the production of plasma cells (PCs), all of which contribute to the production of RABV-specific IgG and virus-neutralizing antibodies (VNAs). Collectively, our work demonstrates that TLR4 is necessary for the recruitment of cDC2 and for the induction of RABV-induced humoral immunity, which is regulated by the cDC2-Tfh-GC B axis. IMPORTANCE Vaccination is the most efficient method to prevent rabies. TLR4, a well-known immune sensor, plays a critical role in initiating innate immune response. Here, we found that TLR4 deficiency ( TLR4 -/- ) mice suppressed the induction of humoral immune response after immunization with rabies virus (RABV), including reduced production of VNAs and RABV-specific IgG, compared with that occurred in wild-type (WT) mice. As a consequence, TLR4 -/- mice exhibited higher mortality than WT mice after challenge with virulent RABV. Importantly, further investigation found that TLR4 signaling promoted the recruitment of cDC2 (CD8α + CD11b - ), a subset of cDCs known to induce CD4 + T cell immunity through their MHC-II presentation machinery. Our results imply that TLR4 is indispensable for an efficient humoral response to rabies vaccine, which provides new insight into the development of novel rabies vaccines.

scholarly journals Humoral Immune Response to Avian Influenza Vaccination Over a Six-Month Period in Different Species of Captive Wild Birds

2008 ◽  
Vol 52 (2) ◽  
pp. 222-228 ◽  
Author(s):  
Maria Furger ◽  
Richard Hoop ◽  
Hanspeter Steinmetz ◽  
Ulrike Eulenberger ◽  
Jean-Michel Hatt
Keyword(s):  
Immune Response ◽  
Avian Influenza ◽  
Influenza Vaccination ◽  
Humoral Immune Response ◽  
Wild Birds ◽  
Humoral Immune

scholarly journals Role of Bordetella bronchisepticaFimbriae in Tracheal Colonization and Development of a Humoral Immune Response

2000 ◽  
Vol 68 (4) ◽  
pp. 2024-2033 ◽  
Author(s):  
Seema Mattoo ◽  
Jeff F. Miller ◽  
Peggy A. Cotter
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Limit Of Detection ◽  
Immunoglobulin M ◽  
Tissue Culture Cell ◽  
Wild Type ◽  
Humoral Immune ◽  
Tract Infections

ABSTRACT Fimbriae are filamentous, cell surface structures which have been proposed to mediate attachment of Bordetella species to respiratory epithelium. Bordetella bronchiseptica has four known fimbrial genes: fim2, fim3,fimX, and fimA. While these genes are unlinked on the chromosome, their protein products are assembled and secreted by a single apparatus encoded by the fimBCD locus. ThefimBCD locus is embedded within the fha operon, whose genes encode another putative adhesin, filamentous hemagglutinin (FHA). We have constructed a Fim− B. bronchiseptica strain, RB63, by introducing an in-frame deletion extending from fimB through fimD. Western blot analysis showed that RB63 is unable to synthesize fimbriae but is unaffected for FHA expression. Using this mutant, we assessed the role of fimbriae in pathogenesis in vitro and in vivo in natural animal hosts. Although RB63 was not significantly defective in its ability to adhere to various tissue culture cell lines, including human laryngeal HEp-2 cells, it was considerably altered in its ability to cause respiratory tract infections in rats. The number of ΔfimBCD bacteria recovered from the rat trachea at 10 days postinoculation was significantly decreased compared to that of wild-type B. bronchiseptica and was below the limit of detection at 30 and 60 days postinoculation. The number of bacteria recovered from the nasal cavity and larynx was not significantly different between RB63 and the wild-type strain at any time point. The ability of fimbriae to mediate initial attachment to tracheal tissue was tested in an intratracheal inoculation assay. Significantly fewer RB63 than wild-type bacteria were recovered from the tracheas at 24 h after intratracheal inoculation. These results demonstrate that fimbriae are involved in enhancing the ability of B. bronchiseptica to establish tracheal colonization and are essential for persistent colonization at this site. Interestingly, anti-Bordetella serum immunoglobulin M (IgM) levels were significantly lower in animals infected with RB63 than in animals infected with wild-type B. bronchiseptica at 10 days postinoculation. Even at 30 days postinoculation, RB63-infected animals had lower serum anti-Bordetella antibody titers in general. This disparity in antibody profiles suggests that fimbriae are also important for the induction of a humoral immune response.

scholarly journals Innate immunity mediator STING modulates nascent DNA metabolism at stalled forks in human cells

2021 ◽  
Author(s):  
Vy N. Nguyen ◽  
Salomé Brunon ◽  
Maria N. Pavlova ◽  
Pavlo Lazarchuk ◽  
Roya D. Sharifian ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Replication Forks ◽  
Wild Type ◽  
Feedback Connection ◽  
Pathway Activation ◽  
Foreign Dna ◽  
Sting Pathway

The cGAS/STING pathway, part of the innate immune response to foreign DNA, is known to be activated by cell's own DNA arising from the processing of the genome, including the excision of nascent DNA at arrested replication forks. We found STING activation to affect nascent DNA processing, suggesting a novel, unexpected feedback connection between the two events. Depletion of STING suppressed and re-expression of the protein in STING-deficient cells upregulated degradation of nascent DNA. Fork arrest was accompanied by the STING pathway activation, and a STING mutant that does not activate the pathway failed to upregulate nascent strand degradation. Consistent with this, cells expressing the STING mutant had a reduced level of RPA on parental and nascent DNA of arrested forks as well as a reduced CHK1 activation compared to the cells with wild type STING. Together our findings reveal a novel connection between replication stress and innate immunity.

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