Page 197 - Veterinary Immunology, 10th Edition

iron binds to transferrin and is carried to erythroblasts for use in
VetBooks.ir new red cell production.

Despite the low availability of iron, bacteria such as M.
tuberculosis, B. anthracis, and E. coli can successfully invade an

animal because they produce their own iron-binding proteins called
siderophores. Mycobacteria use their siderophore (called
carboxymycobactin) to strip iron from mammalian ferritin. S. aureus
uses staphyloferrins to lyse red cells and access the iron in

hemoglobin. Enterochelin is a very potent iron chelator produced
and secreted by many enteric bacteria. When serum iron levels are
elevated, as occurs after red cell destruction, animals become more
susceptible to bacterial infections.

When bacteria invade the body, the body responds by producing
two acute-phase proteins, hepcidin and haptoglobin. Hepcidin is
produced by hepatocytes under the influence of IL-1 and IL-6.
Hepcidin binds to ferroportin and triggers its internalization and

degradation. Hepcidin also suppresses intestinal iron absorption by
downregulating ferroportin expression in enterocytes. In healthy
individuals, hepcidin production is regulated by systemic iron
availability, or by erythropoietic signals and hypoxia. In

inflammation, however, IL-6 and IL-1 stimulate the hepcidin
promoter. As a result, hepcidin increases, ferroportin decreases,
iron absorption by enterocytes is blocked, and macrophages can no
longer export their iron. Iron availability for red blood cell

production drops, and a hypoferremia develops. Chronically
infected animals become anemic—the anemia of infection. This is
usually a mild normocytic, normochromic, nonregenerative anemia.
Haptoglobin is another major acute-phase protein in ruminants,

horses, and cats. It can rise from virtually undetectable levels in
normal calves to as high as 1 mg/mL in calves with acute
respiratory disease. Haptoglobin also binds iron and makes it
unavailable to invading bacteria.

Mammals may also capture iron by stealing bacterial
siderophores. Thus during bacterial infections, the mammalian
liver, spleen, and macrophages synthesize a protein called lipocalin
2. Lipocalin 2 (also called siderocalin) binds the bacterial
siderophore enterochelin with very high affinity. Lipocalin 2 is

essential for limiting the growth of enterochelin-producing bacteria

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