Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 16, Pages -Publisher
MDPI
DOI: 10.3390/ijms22168701
Keywords
chronic granulomatous disease; inflammation; immune; murine model; myeloproliferative disease; NADPH oxidase
Funding
- Regional Government of Castile and Leon [SA077P20]
- Regional Government of Castile and Leon, Spain
- ERDF funds
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The study demonstrates that Cyba(-/-) mice with CGD spontaneously develop granulomas, serving as a valuable model for studying the disease. The altered homeostasis of hematopoiesis in these mice, marked by significant weight loss, splenomegaly, myeloid hyperplasia, and anemia, suggests a possible contribution to the poor outcomes in CGD patients besides their defective innate immunity.
Haematopoiesis is a paradigm of cell differentiation because of the wide variety and overwhelming number of mature blood cells produced daily. Under stress conditions, the organism must adapt to a boosted demand for blood cells. Chronic granulomatous disease (CGD) is a genetic disease caused by inactivating mutations that affect the phagocyte oxidase. Besides a defective innate immune system, CGD patients suffer from recurrent hyper-inflammation episodes, circumstances upon which they must face emergency haematopoiesis. The targeting of Cybb and Ncf1 genes have produced CGD animal models that are a useful surrogate when studying the pathophysiology and treatment of this disease. Here, we show that Cyba(-/-) mice spontaneously develop granuloma and, therefore, constitute a CGD animal model to complement the existing Cybb(-/-) and Ncf1(-/-) models. More importantly, we have analysed haematopoiesis in granuloma-bearing Cyba(-/-) mice. These animals showed a significant loss of weight, developed remarkable splenomegaly, bone marrow myeloid hyperplasia, and signs of anaemia. Haematological analyses showed a sharped decrease of B-cells and a striking development of myeloid cells in all compartments. Collectively, our results show that granuloma inflammatory lesions dramatically change haematopoiesis homeostasis. Consequently, we suggest that besides their defective innate immunity, the alteration of haematopoiesis homeostasis upon granuloma may contribute to the dismal outcome of CGD.
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