PhD student, Rutgers University
Effects of Air Pollution Particulate Matter on Adaptive Antimycobacterial Immunity
The worldwide increase in urban air pollution from growing industrial production and vehicular traffic poses serious threats to global public health. Air pollution particulate matter (PM) may also render large populations vulnerable to Mycobacterium tuberculosis infection (M.tb) and progression to active tuberculosis. My study uses real-world PM and human immune cells to explore the effects of PM on human adaptive immune responses to M.tb and expose the potential risk of PM on lung diseases
Abstract: IFNγ-producing CD4(+) T cells (IFNγ(+)CD4(+) T cells) are the key orchestrators of protective immunity against Mycobacterium tuberculosis (Mtb). Primarily, these cells act by enabling Mtb-infected macrophages to enforce phagosome-lysosome fusion, produce reactive nitrogen intermediates (RNIs), and activate autophagy pathways. However, TB is a heterogeneous disease and a host of clinical and experimental findings has also implicated IFNγ(+)CD4(+) T cells in TB pathogenesis. High frequency of IFNγ(+)CD4(+) T cells is the most invariable feature of the active disease. Active TB patients mount a heightened IFNγ(+)CD4(+) T cell response to mycobacterial antigens and demonstrate an IFNγ-inducible transcriptomic signature. IFNγ(+)CD4(+) T cells have also been shown to mediate TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) observed in a subset of antiretroviral therapy (ART)-treated HIV- and Mtb-coinfected people. The pathological face of IFNγ(+)CD4(+) T cells during mycobacterial infection is further uncovered by studies in the animal model of TB-IRIS and in Mtb-infected PD-1(-/-) mice. This manuscript encompasses the evidence supporting the dual role of IFNγ(+)CD4(+) T cells during Mtb infection and sheds light on immune mechanisms involved in protection versus pathogenesis.
Pub.: 25 Jun '17, Pinned: 04 Oct '17
Abstract: Pediatric tuberculosis (TB) is an underappreciated problem and accounts for 10 % of all TB deaths worldwide. Children are highly susceptible to infection with Mycobacterium tuberculosis and interrupting TB spread would require the development of effective strategies to control TB transmission in pediatric populations. The current vaccine for TB, M. bovis Bacille Calmette-Guérin (BCG), can afford some level of protection against TB meningitis and severe forms of disseminated TB in children; however, its efficacy against pulmonary TB is variable and the vaccine does not afford life-long protective immunity. For these reasons there is considerable interest in the development of new vaccines to control TB in children. Multiple vaccine strategies are being assessed and include recombinant forms of the existing BCG vaccine, protein or viral candidates designed to boost BCG-induced immunity, or live attenuated forms of M. tuberculosis. A number of these candidates have entered clinical trials; however, no vaccine has shown improved protective efficacy compared to BCG in humans. The current challenge is to identify the most suitable candidates to progress from early to late stage clinical trials, in order to deliver a vaccine that can control and hopefully eliminate the global threat of TB.
Pub.: 14 Jul '17, Pinned: 04 Oct '17
Abstract: The major innate immune cell types involved in tuberculosis (TB) infection are macrophages, dendritic cells (DCs), neutrophils and natural killer (NK) cells. These immune cells recognize the TB-causing pathogen Mycobacterium tuberculosis (Mtb) through various pattern recognition receptors (PRRs), including but not limited to Toll-like receptors (TLRs), Nod-like receptors (NLRs) and C-type lectin receptors (CLRs). Upon infection by Mtb, the host orchestrates multiple signaling cascades via the PRRs to launch a variety of innate immune defense functions such as phagocytosis, autophagy, apoptosis and inflammasome activation. In contrast, Mtb utilizes numerous exquisite strategies to evade or circumvent host innate immunity. Here we discuss recent research on major host innate immune cells, PRR signaling, and the cellular functions involved in Mtb infection, with a specific focus on the host's innate immune defense and Mtb immune evasion. A better understanding of the molecular mechanisms underlying host-pathogen interactions could provide a rational basis for the development of effective anti-TB therapeutics.Cellular &Molecular Immunology advance online publication, 11 September 2017; doi:10.1038/cmi.2017.88.
Pub.: 12 Sep '17, Pinned: 04 Oct '17