Mudalagiriyappa, S. | bioRxiv Science

bioRxiv2022

Sialophorin is an essential host element for vaccine immunity against pulmonary fungal infections

The global burden of fungal infections is alarming, primarily due to the increasing immune-compromised population. The immuno-preventive/therapeutic measures, including vaccines, are necessary to prevent or control fungal diseases. Identifying a protective host element as a functional phenotypic marker is immensely valuable. We identified a host element, sialophorin, preferentially associated with antifungal memory T cells. We investigated its role in vaccine immunity using a mouse model of pulmonary fungal infection. We found that sialophorin was essential to bolster CD8+ T-cell responses to the vaccine by enhancing their differentiation and expanding cytokine-producing cells required for immunity. Using a gain-of-function approach, activating sialophorin using mAb augmented the CD8+ T cell responses, and sialophorin-sufficient CD8+ T cells were competitively superior in differentiation and expansion to the deficient cells. Sialophorin-mediated vaccine immunity was independent of the T cell trafficking effect. Finally, we show that sialophorin is a potential functional phenotypic marker of fungal vaccine-potency and immunity. Our study revealed that sialophorin is an essential host-target element to bolster vaccine responses and serves as a potential biomarker of fungal immunity. Author SummaryFungal infections have been rising in recent years due to increased immunocompromised individuals. Vaccination of at-risk individuals helps counter the infections. Thus, suitable vaccine platforms are needed with apt adjuvants, and a phenotypic marker of vaccine immunity will bolster the efforts. We identified a phenotypic marker, sialophorin, associated with T cell vaccine immunity to fungal infection. Our findings show an essential role of sialophorin for fungal immunity, as a target of adjuvanticity, and as a potential biomarker of vaccine immunity against many fungal infections.

immunology↗

bioRxiv2020

Decoding the role of CBLB for innate immune responses regulating systemic dissemination during Non-Tuberculous Mycobacteria infection

Non-Tuberculous Mycobacteria (NTM) are ubiquitous in nature, present in soil and water, and cause primary leading to disseminated infections in immunocompromised individuals. NTM infections are surging in recent years due to an increase in an immune-suppressed population, medical interventions, and patients with underlying lung diseases. Host regulators of innate immune responses, frontiers for controlling infections and dissemination, are poorly defined during NTM infections. Here, we describe the role of CBLB, an E3-ubiquitin ligase, for innate immune responses and disease progression in a mouse model of NTM infection under compromised T-cell immunity. We found that CBLB thwarted NTM growth and dissemination in a time- and infection route- dependent manner. Mechanistically, we uncovered defects in many innate immune cells in the absence of Cblb, including poor responses of NK cells, inflammatory monocytes, and conventional dendritic cells. Strikingly, Cblb-deficient macrophages were competent to control NTM growth in vitro. Histopathology suggested the lack of early formation of granulomatous inflammation in the absence of CBLB. Collectively, CBLB is essential to mount productive innate immune responses and help prevent the dissemination during an NTM infection under T-cell deficiency.

immunology↗