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The Italian War of 1536-38 was a chapter of the Italian Wars that pitted Emperor Charles V's nations of the Holy Roman Empire and Spain against an alliance of France and the Ottoman Empire. Following the death of the childless Duke Francesco II Sforza of Milan and Philip of Habsburg's inheritance of Sforza's lands, King Francis I of France sought to claim the Duchy of Milan for himself. The French allied with the Ottoman Empire in a move that shocked all of Christendom, as the French were now allied to Muslim "heathens".

In March 1536, the French general Philippe de Chabot led an army into Piedmont and conquered Turin. However, the French failed to seize Milan, and Charles V responded by invading Provence in southern France. With the road to Marseille cut, Charles would only be able to advance into further France if he would assault the heavily-fortified stronghold of Avignon, and his troops began to suffer from dysentery after the French soldiers deliberately left over-ripe fruit on the trees near Charles' encampments. Charles decided to retreat into Spain, and Francis' massively-reinforced forces in Italy marched on Genoa. In August 1536, the French army - assisted by an Ottoman fleet - blockaded the heavily-fortified port of Genoa, and the French proceeded to capture several towns in Piedmont. Charles V was squeezed by both the French and the Ottomans, and he was forced to agree to the 18 June 1538 Treaty of Nice. Charles V and Francis I refused to sit in the same room due to their mutual hatred of each other, and Pope Paul III went from room to room as the negotiator. France acquired Turin (Savoy and Piedmont) during the war, and the war entrenched hostilities between France and Spain, while it strengthened the Franco-Ottoman alliance.

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