Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection

Abstract

The variable outcome of viral exposure is only partially explained by known factors. We administered respiratory syncytial virus (RSV) to 58 volunteers, of whom 57% became infected. Mucosal neutrophil activation before exposure was highly predictive of symptomatic RSV disease. This was associated with a rapid, presymptomatic decline in mucosal interleukin-17A (IL-17A) and other mediators. Conversely, those who resisted infection showed presymptomatic activation of IL-17– and tumor necrosis factor–related pathways. Vulnerability to infection was not associated with baseline microbiome but was reproduced in mice by preinfection chemokine-driven airway recruitment of neutrophils, which caused enhanced disease mediated by pulmonary CD8+ T cell infiltration. Thus, mucosal neutrophilic inflammation at the time of RSV exposure enhances susceptibility, revealing dynamic, time-dependent local immune responses before symptom onset and explaining the as-yet unpredictable outcomes of pathogen exposure.

The Effect of RSV Infection on the Respiratory Microbiome of Adults

“…As previously reported, prior to viral inoculation (baseline) [8], there were no significant difference in bacterial alpha diversity (Richness, P = 0.948; Shannon-Weiner, P = 0.263; Simpsons, P = 0.166) or beta diversity (Bray-Curtis dissimilarity, R 2 = 0.055, P = 0.087).…”

“…Thirty-seven healthy non-smoking individuals aged between 18 and 50 years old were recruited into the study (Table 1) [14]. Participants were screened for immunodeficiencies, respiratory diseases and medications [8].…”

“…Day 7 was the peak of viral infection and viral load fell after this point. At Day 28 no patients had any sign of clinical infection and viral load was not measured, as previously described[8].Indicator species analysis and DESeq2 were used to investigate if any individualOTUs were associated with the outcome of viral infection at these time points.At baseline, indicator species and DESeq2 analyses identified several OTUs significantly associated with outcome. Four OTUs were found to overlap between the two analyses.…”

Effects of Environmental Factors on Severity and Mortality of COVID-19

“…Recent studies on the interaction between climate changes and respiratory barrier dysfunction indicated not only higher incidence of viral infection but also higher vulnerability of nasal mucosa through increased incidence of nosebleed in the emergency departments in the conditions of low temperature and low humidity (43). A recently published study that exposed volunteers to respiratory syncytial virus (RSV), one of the pathogens responsible for the common cold, demonstrated that pre-existing inflammation in the respiratory mucosa was a risk factor for infection (44), which further supports the importance of mucociliary dysfunction and respiratory barrier impairment for infection with respiratory viruses.…”

In depth analysis of patients with severe SARS-CoV-2 in sub-Saharan Africa demonstrates distinct clinical and immunological profiles

“…However, there is a paucity of information on immune responses against SARS-CoV-2 infection in the upper airway (17). Minimally invasive sampling techniques of the nasal mucosa are well-tolerated, and highly useful in human challenge models of respiratory syncytial virus and Streptococcus pneumoniae (18, 19). Given importance of the nose in SARS-CoV-2 infection (20), understanding the host–viral interaction at the nasal mucosa could provide additional insights to understand and potentially modulate COVID-19 prognosis.…”