Impact of Host Genetics and Biological Response Modifiers on Respiratory Tract Infections

Abstract

Host susceptibility to respiratory tract infections (RTI) is dependent on both genetic and acquired risk factors. Repeated bacterial and viral RTI, such as pneumonia from encapsulated microorganisms, respiratory tract infections related to respiratory syncytial virus or influenza, and even the development of bronchiectasis and asthma, are often reported as the first symptom of primary immunodeficiencies. In the same way, neutropenia is a well-known risk factor for invasive aspergillosis, as well as lymphopenia for Pneumocystis , and mycobacterial infections. However, in the last decades a better knowledge of immune signaling networks and the introduction of next generation sequencing have increased the number and diversity of known inborn errors of immunity. On the other hand, the use of monoclonal antibodies targeting cytokines, such as tumor necrosis factor alpha has revealed new risk groups for infections, such as tuberculosis. The use of biological response modifiers has spread to almost all medical specialties, including inflammatory diseases and neoplasia, and are being used to target different signaling networks that may mirror some of the known immune deficiencies. From a clinical perspective, the individual contribution of genetics, and/or targeted treatments, to immune dysregulation is difficult to assess. The aim of this article is to review the known and newly described mechanisms of impaired immune signaling that predispose to RTI, including new insights into host genetics and the impact of biological response modifiers, and to summarize clinical recommendations regarding vaccines and prophylactic treatments in order to prevent infections.

Angiotensin‐converting enzyme 2 (ACE2), SARS‐CoV‐2 and the pathophysiology of coronavirus disease 2019 (COVID‐19)

“…Immunomodulating drugs or biological response modifiers alter the host immune system by interacting with a specific target crucial for disease pathogenesis [207]. Many of these compounds enrich the therapeutic armamentarium of several malignancies, autoimmune disorders, transplantation rejection, as well as infectious diseases.…”

Triple RNA-Seq Reveals Synergy in a Human Virus-Fungus Co-infection Model

“…Additionally, triple RNA-seq may be harnessed to investigate the influence of immunosuppressive drugs on co-infected cells or to test how co-infection affects the dendritic cell's ability to cross-present antigens from each pathogen to T cells. Finally, multi-organism RNA-seq holds great promise for expanding our understanding of immune dysregulation in other polymicrobial infections, including post-influenza aspergillosis (Lacoma et al, 2019;Vanderbeke et al, 2018), multifaceted microbial interactions in patients with cystic fibrosis (Sass et al, 2019), or-up-to-the-minute-invasive fungal infections of critically ill coronavirus disease 2019 (COVID-19) patients (Koehler et al, 2020).…”

Genotypic and Phenotypic Characterization of Staphylococcus aureus Isolates from the Respiratory Tract in Mechanically-Ventilated Patients

“…There was no statistical significance between Hla expression and cytotoxicity and adhesion values ( Figure 5D,E). 28,41,46,103,116,121,126,133,146, 184 and 185) and for 5 cases all isolates were Hla negative (Patient ID 17, 32, 50, 124 and 181). For two cases (Patient ID 15 and 54), Hla wa initially detected but later no expression was reported, and in two cases (Patient ID 48, 59 144 and 193), Hla was initially absent but later reported.…”

“…For ID146 and 181, ST were clustered in two different clinical episodes, while for the remaining one (ID15), both ST were simultaneously detected during the same episode. For the following ID cases (ID 36,37,41,59,115,126 and 193), although strains presented the same ST (considering each patient individually), the gene profile displayed some differences (presence/absence of a selected gene) ( Figure 1). Table 1.…”

“…There is one case (Patient ID 4) that was considered persistent but isolates available for genotypic and phenotypic characterization were a nasal swab and a blood culture. For 16 cases, there were no changes in Hla expression: in 12 cases all isolates were Hla positive (Patient ID 9,28,41,46,103,116,121,126,133,146, 184 and 185) and for 5 cases all isolates were Hla negative (Patient ID 17, 32, 50, 124 and 181). For two cases (Patient ID 15 and 54), Hla was initially detected but later no expression was reported, and in two cases (Patient ID 48, 59, 144 and 193), Hla was initially absent but later reported.…”