Biology subjects

Karan, S.

Publications and source records attributed to Karan, S..

3 recordsLinked to original sources

bioRxiv2026

Tissue-Resident and Effector-Memory Lymphocyte Recruitment to the Ocular Mucosa Requires CCL28/CCR10 Signaling During Recurrent HSV-1 Infection

Ocular herpes simplex virus type 1 (HSV-1) infection is a major cause of infectious corneal disease that can lead to recurrent herpetic keratitis, chronic inflammation, and vision loss. Although effective antiviral immunity is essential for controlling HSV-1 and limiting recurrent disease, the mechanisms regulating recruitment of protective lymphocytes to the ocular mucosa remain incompletely understood. CCL28 is a mucosa-associated chemokine expressed at epithelial surfaces that signals through its receptor CCR10, expressed by distinct antiviral T- and B-cell subsets. Using a mouse model of recurrent ocular HSV-1 infection, we investigated the role of the CCL28/CCR10 axis in mobilizing protective HSV-1-specific immune cells to the ocular mucosa (OM). Following infection, wild-type (WT) B6 mice showed a marked increase in CCL28 expression within the OM, coinciding with accumulation of HSV-specific effector-memory (CCR10+CD44+CD62L-) T cells and CCR10+B220+ B cells in the OM and trigeminal ganglia (TG). These cells displayed an antigen-experienced, effector-memory phenotype, suggesting that CCL28/CCR10 signaling contributes to a localized antiviral immune response in the ocular mucosa. By contrast, CCL28-deficient (CCL28(-/-)) mice: (i) were more susceptible to recurrent ocular HSV-1 infection; (ii) exhibited significantly reduced frequencies of HSV-specific effector-memory (CCR10+CD44+CD62L-) and tissue-resident memory (CCR10+CD69+CD103+) T cells, as well as CCR10+B220+ B cells, in the infected OM and TG; and (iii) showed diminished effector function (IFN-{gamma}, TNF, and Granzyme B production) in these populations, associated with increased viral burden and ocular pathology. These findings identify the CCL28/CCR10 axis as a critical regulator of antiviral B- and T-cell trafficking to the ocular mucosa, contributing to protection against recurrent herpetic eye disease and providing a mechanistic basis for targeting mucosal chemokine pathways to improve vaccine strategies against ocular herpes.

immunology↗

bioRxiv2026

Symbiont-mediated shifts in cuticular hydrocarbon profiles reduce female attractiveness after mating

Males can influence future mating interactions of females after copulation by changing female signals that subsequent males will encounter. In insects, such effects commonly involve cuticular hydrocarbons (CHCs), but whether heritable microbial symbionts contribute to post-mating chemical signalling remains largely unknown. Kelly's citrus thrips, Pezothrips kellyanus, provides an ideal system to address this question because reproductive compatibility is shaped by common arthropod endosymbionts. Across P. kellyanus populations, Cardinium occurs in almost all individuals whereas Wolbachia varies in prevalence and appears to spread by cytoplasmic incompatibility (CI). Yet, females with only Cardinium (C) avoid incompatible males carrying both Cardinium and Wolbachia (CW), and this discrimination is linked to the distinct CHC profile of CW males. Here, we tested whether this endosymbiont-associated male perfume persists on females beyond copulation by altering the female CHC profile and subsequent male mating behaviour. Using behavioural assays and GC-MS-based CHC profiling, we found that, independent of female endosymbiont association, females first mated with CW males received fewer antennal contacts and mating attempts from subsequent C males. Furthermore, mating remodelled female CHC profiles, while mating with CW males produced a distinctive post-mating chemical signature. Most notably, tridecane, previously detected only in CW males, occurred exclusively in females mated with CW males. Our findings show that endosymbionts can alter mated female CHCs and influence future sexual communication between male and female hosts. These findings reveal a previously unrecognised post-mating route through which endosymbionts reshape sexual communication, with potential consequences for reproductive compatibility and symbiont transmission dynamics.

evolutionary biology↗

bioRxiv2025

CXCL13/CXCR5 Chemokine Axis Promotes CXCR5+CD19+ B-Cell and Follicular/Effector CXCR5+CD4+ T-Cell Responses in the Lungs Associated with Protection from Severe and Fatal COVID-19 Following Infection with Pathogenic SARS-CoV-2 Delta Variant

Chemokines play an important role in shaping lung innate and adaptive immunity to pulmonary infections and diseases. However, the role of CXC ligand 13 (CXCL13), a chemokine homeostatically produced by various lung cell types, in the protection from SARS-CoV-2 infection and disease remains controversial. Some studies reported that asymptomatic patients who survived severe COVID-19 had CXCL13-dominated mucosal immune responses in the lungs early during infection. In contrast, other studies reported that a high level of CXCL13 was associated with severity and mortality in COVID-19 patients. In this study, to determine the direct role of CXCL13 in SARS-CoV-2 infection and disease, we generated CXCL13-/-K18-hACE2 mice, that are both transgenic for ACE2 and deficient in CXCL13 and compared their infection and COVID-19-like disease symptoms with those in wild-type K18-hACE2 transgenic mouse littermates following intranasal inoculation with the pathogenic SARS-CoV-2 delta variant (B.1.617.2). Compared to age- and gender-matched SARS-CoV-2 infected wild-type K18-hACE2 mice, SARS-CoV-2 infected CXCL13-/-K18-hACE2 deficient mice exhibited (i) higher viral load in the lungs; (ii) severe COVID-19-like lung pathology; (iii) exacerbated weight loss; (iv) increased mortality. The apparent severe COVID-19-like symptoms in CXCL13-/-K18-hACE2 deficient mice were associated with: (i) significantly lower frequencies of functional lung-resident C-X-C chemokine receptor 5+ (CXCR5)+CD19+ B cells, follicular CXCR5+CD4+ helper T cells (Tfh cells), and IFN-{psi}+TNF-+GzmB+Ki67+effector CD4+ Th1 cells; and (ii) a significant reduction in the levels of SARS-CoV-2-Spike specific Th1 associated IgG1 and IgG2b antibody isotypes. These findings corroborate previous human reports suggesting a critical role of the CXCL13/CXCR5 chemokine axis in the protective B- and T-cell mucosal immunity to SARS-CoV-2 infection and disease, offering a potential new immunotherapeutic target for treatment.

immunology↗