- How do viral infections impact immune competence in the respiratory mucosa and how can this knowledge translate into better therapeutic strategies to reduce susceptibility to lower respiratory tractinfections (LRTIs) in SSA?
- What is the effect of persistent HIV-infection in the lung during potent antiretroviral therapy (ART) and how can this be mitigated?
Viral infections are very common in SSA and are associated with a higher burden of opportunistic diseases. HIV impairs multiple aspects of host immunity resulting in a high risk of lower respiratory infections in HIV-infected individuals. CMV and EBV promote immune exhaustion leading to impaired immune responses. Influenza virus infection modulates host immunity leading to increased susceptibility to secondary bacterial infection. These observations strongly suggest that viral infections alter the host immune competence, however, our current understanding of immune mechanisms underlying the increased risk in areas of high disease burden is incomplete.We have shown that HIV persists in the lung in individuals on potent ART with undetectable plasma viraemia, suggesting that the lung represents an under-appreciated HIV reservoir. We have also shown Mycobacterium tuberculosis-specific CD4 T cell immunity in the lung is not fully reconstituted in HIV-infected adults on ART, however, whether this is due to persistence of HIV in the lung or other factors, remains to be elucidated. Furthermore, we have shown that FLU-specific CD4 T cell responses are impaired in Malawian HIV-infected adults and the surveillance studies at MLW have in parallel shown increased severity and duration of influenza illness in this group. However, the immunological correlates of influenza viral clearance that predict severity and duration of influenza illness in HIV-infected individuals are not well understood.
- a) Identification of specific HIV-mediated defects in immune competence of the lung that favour progression of LRTIs; b) Investigation of immunological correlates of influenza viral clearance that predict severity and duration of influenza illness in HIV-infected Malawian adults; c) Molecular and phenotypic characterization of lung memory CD4 T cells
- Characterisation of the cellular and viral mechanisms for HIV persistence in the lung; b) Investigation of the association between intrapulmonary anti-retroviral drug concentration and HIV viral load in the lung
Selected publications: Pennington et al., J Infect Dis. 2016, Longwe et al. PLoS One. 2015, Jambo et al., Mucosal Immunol 2014, Jambo et al., Am J Respir Crit Care Med 2014, Jambo et al., Thorax 2011;