Immune Defense in Upper Airways: A Single-Cell Study of Pathogen-Specific Plasmablasts and Their Migratory Potentials in Acute Sinusitis and Tonsillitis

Abstract

BackgroundDespite the high frequency of upper respiratory tract (URT) infections and use of the nasal mucosa as route for vaccination, the local immune mechanism and dissemination of effector lymphocytes from the URT have been insufficiently characterized. To devise a single-cell approach for studying the mucosal immune response in the URT, we explored URT-originating B effector lymphocytes in the circulation of patients with one of two common respiratory infections, acute sinusitis or tonsillitis.MethodsPatients with acute sinusitis (n = 13) or tonsillitis (n = 11) were investigated by ELISPOT for circulating pathogen-specific antibody-secreting cells (ASCs) of IgA, IgG and IgM isotypes approximately one week after the onset of symptoms. These cells’ potential to home into tissues was explored by assessing their expression of tissue-specific homing receptors α4β7, L-selectin, and cutaneous lymphocyte antigen (CLA).ResultsPathogen-specific ASCs were detected in the circulation of all patients, with a geometric mean of 115 (95% CI 46–282) /106 PBMC in sinusitis, and 48 (27–88) in tonsillitis. These responses were mainly dominated by IgG. In sinusitis α4β7 integrin was expressed by 24% of the ASCs, L-selectin by 82%, and CLA by 21%. The proportions for tonsillitis were 15%, 80%, and 23%, respectively. Healthy individuals had no ASCs.ConclusionsURT infections–acute sinusitis and tonsillitis–both elicited a response of circulating pathogen-specific plasmablasts. The magnitude of the response was greater in sinusitis than tonsillitis, but the homing receptor profiles were similar. Human nasopharynx-associated lymphoid structures were found to disseminate immune effector cells with a distinct homing profile.

Circulating pathogen-specific plasmablasts in female patients with upper genital tract infection

“…This is the first study to show that pathogen-specific plasmablasts emerge in the human circulation in response to acute bacterial upper FGT infection, a result according with previous findings for infections at other mucosal sites (Kantele et al 1988(Kantele et al , 1994Palkola et al 2012Palkola et al , 2016. Detecting such cells also in upper FGT infections encourages their use as tools for evaluating immune responses in the FGT.…”

“…As plasmablasts only circulate transiently before homing into their target tissues, sampling timing is critical. We utilized our previous experience of acute mucosal infections in the urinary (Kantele et al 2008) and respiratory tracts (Palkola et al 2012(Palkola et al , 2016, and the gut (Kantele et al1988), and the kinetics of plasmablasts in the circulation as reported in gastroenteritis (Kantele, 2012) and after oral (Kantele, 1990(Kantele, ,1991Kantele et al 1986) and rectal vaccinations (Kantele et al 1998). Antigen-specific plasmablasts enter the blood approximately on the third day after antigen encounter, peak in frequency on day seven, and disappear gradually by days 14-16.…”

“…al. 1986), rectal (Kantele et al 1998;Kutteh et al 2001), or intranasal vaccinations (Quiding-Järbrink et al1997, and in various mucosal infections such as gastroenteritis (Kantele et al 1988(Kantele et al , 2008Kantele JM et al 1996a;Pakkanen et al 2010), pyelonephritis and cystitis (Kantele et al 1994(Kantele et al , 2008, and tonsillitis, sinusitis, and pneumonia (Palkola et al 2012(Palkola et al , 2016. Thus far, circulating plasmablasts have not been explored in acute bacterial infection in the genital tract.…”

“…Lymphocytes typically home back to sites where the antigen was initially encountered (Sigmundsdottir and Butcher, 2008). Accordingly, after intestinal antigen encounter, a high proportion of plasmablasts express  and lower proportions L-selectin (Kantele et al 1997;Kantele JM et al 1996a;Quiding-Järbrink et al 1997) or CLA (Kantele et al 2003), while antigen encounter at other mucosal sites elicits a different homing profile (Kantele et al 2008;Palkola et al 2015Palkola et al , 2016Quiding-Järbrink et al 1997). Likewise, in mice, the set of receptors operating in the homing process differs between the various mucosal sites (e.g.…”

Assessment of an Antibody-in-Lymphocyte Supernatant Assay for the Etiological Diagnosis of Pneumococcal Pneumonia in Children

“…These ALS responses were found to be positively associated with age and serum antibody concentrations, and were higher from cells from adenoids colonized by pneumococci (Zhang et al, 2002(Zhang et al, , 2006. Our data suggest that NP carriage of pneumococci in pneumonia-without apparent pneumococcal disease (Palkola et al, 2012(Palkola et al, , 2016)-also induces IgG secretion from antibodysecreting cells, thus confounding the utility of an ALS-based diagnostic approach.…”