Immune cellular networks underlying recovery from influenza virus infection in acute hospitalized patients

Abstract

How innate and adaptive immune responses work in concert to resolve influenza disease is yet to be fully investigated in one single study. Here, we utilize longitudinal samples from patients hospitalized with acute influenza to understand these immune responses. We report the dynamics of 18 important immune parameters, related to clinical, genetic and virological factors, in influenza patients across different severity levels. Influenza disease correlates with increases in IL-6/IL-8/MIP-1α/β cytokines and lower antibody responses. Robust activation of circulating T follicular helper cells correlates with peak antibody-secreting cells and influenza heamaglutinin-specific memory B-cell numbers, which phenotypically differs from vaccination-induced B-cell responses. Numbers of influenza-specific CD8+ or CD4+ T cells increase early in disease and retain an activated phenotype during patient recovery. We report the characterisation of immune cellular networks underlying recovery from influenza infection which are highly relevant to other infectious diseases.

Robust and prototypical immune responses toward influenza vaccines in the high-risk group of Indigenous Australians

“…IgA expression was determined as (CD19 + IgD − IgM − IgG − ) as validated previously ( 9 ). This supports our previous study where vaccination did not induce marked changes to the isotype distribution of influenza-specific B cells ( 9 ) but is in contrast to influenza virus infection where both IgG + and IgA + HA-specific B cells were prominent during acute infection, before becoming predominantly IgG + at the convalescent phase ( 26 ). Taken together, vaccination induced the expansion of activated memory HA-specific B cells which were predominantly IgG + in both Indigenous and non-Indigenous donors.…”

“…Moreover, seroconverters for H1, H3, or IBV had significantly higher fold changes in HA-specific B cells (percent after/percent before) compared with nonserocoverters. Postvaccination, these memory HA-specific B cells increased in activated memory phenotype and were predominantly IgG + , reminiscent of prototypical vaccine-induced immune responses in our previous study ( 9 ) but in contrast to acute influenza virus infection which comprises both IgG + and IgA + HA-specific B cells before becoming IgG + at the recovery phase ( 26 ). Our data provide evidence that QIV induces activation and increases of influenza-specific B cells in Indigenous Australians, crucial for the formation of memory and the protective effect of vaccination.…”

Lung-Resident Memory CD8+ T Cells in Human Influenza: How Innate Are They?

“…Perhaps then we could carefully delineate the types of T cells comprising the spectrum of innate-like and more adaptive-like CD8 + T-cell subsets, which can include innate T lymphocytes such as mucosal-associated invariant T (MAIT) cells and natural killer T cells. The role of innate T lymphocytes during influenza disease was previously suggested, with higher numbers of functional MAIT and T cells in the blood being associated with reduced disease severity in hospitalized patients with influenza ( 11 ). Another idealistic approach could be the use of highly sophisticated spatial transcriptomics ( 12 ) with endobronchial tissue samples.…”

“…However, the BAL tetramer + CD8 + T cells were of much higher frequencies (up to 4–5% of CD8 + T cells) compared with <1% in the blood during infection, similar to the authors’ previous RSV infection study ( 6 ) and the postmortem influenza studies ( 7 – 9 ). Nguyen and colleagues also observed low influenza tetramer + CD4 + and CD8 + T-cell frequencies of <1% in the peripheral blood, characterized by highly activated HLA-DR, CD38, PD-1, or CD71 phenotypes, in patients hospitalized with influenza disease ( 11 ). The authors hypothesized that larger numbers could be migrating to the respiratory tract during acute infection.…”

“…Although the authors performed tetramer staining in a small number of the available HLA-A1 + and HLA-A2 + BAL samples, which they diligently acknowledge in the article, the quality of tetramer staining is very convincing. In future studies, it would be enticing to include additional tetramers encompassing a range of influenza class I epitopes spanning several different common HLAs ( 11 ) to understand their immunodominance hierarchy and perhaps class II epitopes to examine the role of CD4 + T cells at the site of infection. However, the technical requirements for generating peptide-MHC tetramers or the high costs of purchasing these reagents and HLA typing of the participants remain considerable factors here.…”