Neutrophils are the most abundant of the circulating immune cells and are the first to be recruited to sites of inflammation. Neutrophils are a heterogeneous group of immune cells from which are derived extracellular traps (NETs), reactive oxygen species, cytokines, chemokines, immunomodulatory factors, and alarmins that regulate the recruitment and phenotypes of neutrophils, macrophages, dendritic cells, T cells, and B cells. In addition, cytokine-stimulated neutrophils can express class II major histocompatibility complex and the internal machinery necessary for successful antigen presentation to memory CD4⁺ T cells. This may be relevant in the context of vaccine memory. Neutrophils thus emerge as orchestrators of immune responses that play a key role in determining the outcome of infections, vaccine efficacy, and chronic diseases like autoimmunity and cancer. This review aims to provide a synthesis of current evidence as regards the role of these functions of neutrophils in homeostasis and disease.

Introduction: The Bacille Calmette-Guerin (BCG) vaccine is widely administered in countries with high tuberculosis (TB) prevalence to protect against severe forms of childhood TB. Despite its efficacy, the vaccine can lead to adverse effects like BCGosis, a severe but rare condition marked by systemic granulomatous inflammation. This is because the vaccine is comprised of attenuated BCG bacteria which has the potential to cause uncontrolled dissemination beyond the injection site. Immunocompromised children are particularly vulnerable to this side effect. Through a systematic review of the current literature, this analysis seeks to determine the global incidence of BCGosis and identify critical risk factors associated with its onset. Methods: The review was conducted in accordance with the PRISMA-2020 guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The review’s objectives and scope were framed using the PICOS (Population, Intervention, Comparison, Outcomes and Study Design) framework. Results: Not surprisingly, BCGosis is most prevalent in infants with underlying genetic immunodeficiencies such as severe combined immunodeficiency (SCID) and chronic granulomatous disease (CGD). We found a high correlation between the development of BCGosis and genetic mutations affecting certain immune processes, notably those involved in NADPH oxidase function and interferon-gamma signalling. The risks of developing these mutations also correlated with the prevalence of consanguinity, a common practice in certain populations. Factors like early neonatal vaccination (often within the first week of life) and variations in BCG strains may also influence BCGosis risk. Conclusion: There is an urgent need for enhanced pre-vaccination screening for genetic and immunologic vulnerabilities in infants at hight risk for BCGosis, particularly in populations with high consanguinity rates. Alternatively, considerations should be made as to modifying existing vaccination schedules or postponing BCG immunization until immune competency can be confirmed in these high risk groups.