Pathogen-Specific Immune Fingerprints during Acute Infection: The Diagnostic Potential of Human γδ T-Cells

The last 200 years have seen a dramatic reduction in the prevalence and severity of microbial infections, due to the implementation of groundbreaking measures ranging from improved sanitation and hygiene and the introduction of aseptic techniques to the development of successful vaccines and the discovery of effective antibiotics. Devastating infections that were common until the late nineteenth century such as cholera, diphtheria, plague, syphilis, tuberculosis, and typhoid came into the reach of effective control, at least in developed countries, and with a minimized risk of wound infections surgical procedures began to revolutionize modern medicine. Antibiotics, in particular, radically transformed the treatment and prevention of microbial infections and have saved millions of lives since their introduction (1). However, antibiotic usage is invariably linked to the selective pressure it exerts on the target organism to develop escape strategies (2). We are at present witnessing how the pendulum begins to swing backwards, with anti-microbial resistances developing on an unprecedented global scale. New classes of Gram-positive and Gramnegative “superbugs” are emerging and spreading at an alarming rate, some of which are virtually insusceptible to all available drugs (3–5). The once apocalyptic vision of a “post-antibiotic era” where common infections and minor injuries may result untreatable and eventually fatal is rapidly becoming a real possibility (1, 2, 6, 7), heralding what Margaret Chan, Director-General of the WHO, in 2012 called “the end of modern medicine as we know it.” The appearance of multidrugresistant bacteria has been identified by the WHO, the Centers for Disease Control and Prevention (CDC) in the USA and their European counterpart, the ECDC, as one of the major global health challenges humankind is facing in the twentyfirst century (8–10). According to Sally Davies, the UK Chief Medical Officer, “there are few public health issues of greater importance than anti-microbial resistance in terms of impact on society” (11). There is now an urgent call for antimicrobial stewardship programs that aim to prescribe antibiotics more prudently, and to tailor their use to defined patient groups who will benefit most. The fact that the prevalence of resistance appears to correlate directly with antibiotic consumption across different countries (12) argues in favor of the immediate effectiveness of such tightly controlled programs. As highlighted in a recent Outlook issue in Nature, “the potential to save lives with faster and more targeted diagnoses, decrease unnecessary and often incorrect prescriptions, and even help identify early on where bacterial resistance could occur, will have a drastic effect on the way patients are treated” (13).