The Effects of Macrophage Polarity on Influenza Virus Replication and Innate Immune Responses

Different pathways of macrophage differentiation and activation lead to diverse macrophage phenotypes including expression of cell surface molecules, cytokine secretion and transcription profiles. Here we investigated in vitro the impact of inflammatory or anti-inflammatory polarization of human primary macrophages on their susceptibility to Influenza A virus infection and characterised innate immune responses in infected cells. M2 M-CSF+IL4 macrophages showed greater susceptibility to influenza A infection than M1 GM-CSF+interferon (IFN)γ macrophages.published_or_final_versio

Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus

Public health risks associated to infection by human coronaviruses remain considerable and vaccination is a key option for preventing the resurgence of severe acute respiratory syndrome coronavirus (SARS-CoV). We have previously reported that antibodies elicited by a SARS-CoV vaccine candidate based on recombinant, full-length SARS-CoV Spike-protein trimers, trigger infection of immune cell lines. These observations prompted us to investigate the molecular mechanisms and responses to antibody-mediated infection in human macrophages.published_or_final_versio

Antibody-dependent enhancement of SARS coronavirus infection and its role in the pathogenesis of SARS

1. Anti-SARS-CoV spike antibodies promote infection of primary human immune cells by SARS-CoV. 2. The antibody-dependent enhancement (ADE) infection pathway grants SARS-CoV an opportunity to infect primary human macrophages, but it does not sustain productive viral replication in the infected cells. 3. ADE of SARS-CoV infection does not alter pro-inflammatory gene expression profile of primary human macrophages. 4. Infectivity of SARS-CoV does not rely solely on the potency of target cells to bind — via Fcγ receptor II (CD32) — infectious immune complexes, but depends on the properties of the intracellular domain of the FcγRII. 5. Occurrence of ADE of SARS-CoV infection into human primary macrophages, without alteration to their pro-inflammatory properties, advocates cautious development of SARS-CoV vaccine in humans, and provides new ways of investigation to understand the pathogenesis of SARS.published_or_final_versio

Monitoring by flow cytometry of antigen-specific proliferative response of mouse spleen cells

Topic: Basic aspects of both innate and adaptive immunity, with particular attention to molecular mechanisms involved in pathogen sensin

Antibody-Dependent Enhancement (ADE) of infection and its possible role in the pathogenesis of influenza

Poster Presentation: Theme 5 - Infection & Immunology: 5.0

Investigation of Antibody-Dependent Enhancement (ADE) of SARS Coronavirus Infection and Its Role in Pathogenesis of SARS

Poster presentation - Session: Resp. disease

Toll-like receptor 10 is involved in induction of innate immune responses to influenza virus infection

Toll-like receptors (TLRs) play key roles in innate immune recognition of pathogen-associated molecular patterns of invading microbes. Among the 10 TLR family members identified in humans, TLR10 remains an orphan receptor without known agonist or function. TLR10 is a pseudogene in mice and mouse models are noninformative in this regard. Using influenza virus infection in primary human peripheral blood monocyte-derived macrophages and a human monocytic cell line, we now provide previously unidentified evidence that TLR10 plays a role in innate immune responses following viral infection. Influenza virus infection increased TLR10 expression and TLR10 contributed to innate immune sensing of viral infection leading to cytokine induction, including proinflammatory cytokines and interferons. TLR10 induction is more pronounced following infection with highly pathogenic avian influenza H5N1 virus compared with a low pathogenic H1N1 virus. Induction of TLR10 by virus infection requires active virus replication and de novo protein synthesis. Culture supernatants of virus-infected cells modestly up-regulate TLR10 expression in nonvirus-infected cells. Signaling via TLR10 was activated by the functional RNA-protein complex of influenza virus leading to robust induction of cytokine expression. Taken together, our findings identify TLR10 as an important innate immune sensor of viral infection and its role in innate immune defense and immunopathology following viral and bacterial pathogens deserves attention