Histoplasmosis is a fungal infection caused by Histoplasma capsulatum. Symptoms of this infection vary greatly, but the disease affects primarily the lungs. Occasionally, other organs are affected; called disseminated histoplasmosis, it can be fatal if left untreated. Histoplasmosis is common among AIDS patients because of their suppressed immunity. In immunocompetent individuals, past infection results in partial protection against ill effects if reinfected. Histoplasma capsulatum is found in soil, often associated with decaying bat guano or bird droppings. Disruption of soil from excavation or construction can release infectious elements that are inhaled and settle into the lung. From 1938 to 2013 in the US, 105 outbreaks were reported in a total of 26 states plus Puerto Rico. In 1978 to 1979 during a large urban outbreak in which 100,000 people were exposed to the fungus in Indianapolis, victims had pericarditis, rheumatological syndromes, esophageal and vocal cord ulcers, parotitis, adrenal insufficiency, uveitis, fibrosing mediastinitis, interstitial nephritis, intestinal lymphangiectasia, and epididymitis. Histoplasmosis mimics colds, pneumonia, and the flu, and can be shed by bats in their feces. Signs and symptoms
If symptoms of histoplasmosis infection occur, they start within 3 to 17 days after exposure; the typical time is 12–14 days. Most affected individuals have clinically silent manifestations and show no apparent ill effects. The acute phase of histoplasmosis is characterized by nonspecific respiratory symptoms, often cough or flu-like. Chest X-ray findings are normal in 40–70% of cases.
Pancreatic cancer
In a mice model, administering IRAK4 reduced inflammatory signaling, after which T-cells began to attack tumors and immunotherapy became more effective. Drug target
A common concern with IRAK4 drug therapy or knockdown is if its absence would result in unbearable side effects considering IRAK4 plays an extremely central role in the TLR signalling pathway. Children with IRAK4 deficiency have been found to have decreased immunity to some specific bacterial infections yet not to viral, parasitic or other microbe infections. However, as these children enter adulthood and maternal antibodies are no longer present, susceptibility to infections becomes a rarity. In one study, no significant bacterial infections were documented in all investigated patients over the age of 14 with IRAK4 deficiency. This may mean that in later stages of life, IRAK4 inhibition could provide benefits against certain diseases while maintaining immunity.The next step in this area of research is the formation of safe IRAK4 inhibitors. There has been modest progress in the development of some potential inhibitors of IRAK4 in which their mechanism works by blocking its tyrosine gated ATP binding site. As of 2007 All potential drugs are in the early preclinical stages of development.Early-stage clinical trials of an IRAK4 inhibitor had started by 2019. Moreover, IRAK4 protein degraders have recently entered clinical trials, most notably one from Kymera Therapeutics. References
External links
IRAK4+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
Overview of all the structural information available in the PDB for UniProt: Q9NWZ3 (Human Interleukin-1 receptor-associated kinase 4) at the PDBe-KB.