Valley fever, caused by inhaling the fungal pathogen Coccidioides, presents asignificant public health concern. Coccidioides grows in the soil as mycelia segments and differentiates into arthroconidia (spores) under dry conditions. When the soil is disrupted and aerosolized, it can be inhaled and cause life-threatening lung infections. Originally native to California, Arizona, Mexico, and parts of Central and South America, Coccidioides has expanded due to climate change, reaching non-endemic areas such as Washington State and predicted to advance further into the central United States. Despite 60% of patients being asymptomatic or displaying minimal disease, the remaining 40% face prolonged health complications. Attempts to develop a human vaccine have been hindered by gaps in understanding how the fungus interacts with the immune system and the lung microenvironment. Pro-inflammatory and anti-fungal responses offer protection, yet the mechanism and cellular details are largely unexplored. Alveolar macrophages, acting as the frontline defense in the lungs, are thought to play a pivotal role in initiating a pro-inflammatory response crucial for the clearance of Coccidioides. Neutrophils, the most abundant cells in the body, exhibit rapid reactivity to microbes throughout the human body. These primary cell types are followed by the recruitment of macrophages to infection sites, contributing to an effective immune response. Considering these intricate interactions, my thesis focuses on investigating the initial immunological response of neutrophils and macrophages and developing comprehensive protocols to explore granulomas formation and disease. This thesis work aimed to unravel the complexities of how the immune system regulates Coccidioides infections, offering valuable insights for the development of vaccines and therapeutic strategies.